Peroxisome proliferator-activated receptor γ inhibits pulmonary hypertension targeting store-operated calcium entry
Abstract In this study, we investigated the role of peroxisome proliferator-activated receptor γ (PPARγ) on store-operated calcium entry (SOCE) and expression of the main store-operated calcium channel (SOCCs) components, canonical transient receptor potential (TRPC) in chronic hypoxia (CH)-induced...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Wang, Yingfeng [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2014 |
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| Schlagwörter: |
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| Anmerkung: |
© Springer-Verlag Berlin Heidelberg 2014 |
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| Übergeordnetes Werk: |
Enthalten in: Journal of molecular medicine - Berlin : Springer, 1922, 93(2014), 3 vom: 14. Nov., Seite 327-342 |
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| Übergeordnetes Werk: |
volume:93 ; year:2014 ; number:3 ; day:14 ; month:11 ; pages:327-342 |
| Links: |
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| DOI / URN: |
10.1007/s00109-014-1216-4 |
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| Katalog-ID: |
SPR000767212 |
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| 100 | 1 | |a Wang, Yingfeng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Peroxisome proliferator-activated receptor γ inhibits pulmonary hypertension targeting store-operated calcium entry |
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| 520 | |a Abstract In this study, we investigated the role of peroxisome proliferator-activated receptor γ (PPARγ) on store-operated calcium entry (SOCE) and expression of the main store-operated calcium channel (SOCCs) components, canonical transient receptor potential (TRPC) in chronic hypoxia (CH)-induced pulmonary hypertension (CHPH) rat models. Small interfering RNA (siRNA) knockdown and adenoviral overexpression strategies were constructed for loss-of-function and gain-of-function experiments. PPARγ agonist rosiglitazone attenuates the pathogenesis of CHPH and suppresses Hif-1α, TRPC1, TRPC6 expression in the distal pulmonary arteries (PA), and SOCE in freshly isolated rat distal pulmonary arterial smooth muscle cells (PASMCs). By comprehensive use of knockdown and overexpression studies, and bioinformatical analysis of the TRPC gene promoter and luciferase reporter assay, we demonstrated that PPARγ exerts roles of anti-proliferation, anti-migration, and pro-apoptosis in PASMCs, likely by inhibiting the elevated SOCE and TRPC expression. These effects were inhibited under the conditions of hypoxia or Hif-1α accumulation. We also found that under hypoxia, accumulated Hif-1α protein acts as upstream of suppressed PPARγ level; however, targeted PPARγ rescue acts as negative feedback on suppressing Hif-1α level and Hif-1α mediated signaling pathway. PPARγ inhibits CHPH by targeting SOCE and TRPC via inhibiting Hif-1α expression and signaling transduction. Key messages Rosiglitazone protects PH by normalizing RVSP but not right ventricle hypotrophy.PPARγ inhibits PASMCs proliferation via targeting SOCE and TRPC by suppressing Hif-1α.PPARγ and Hif-1α share mutual inhibitory regulation in PASMCs.PPARγ restoration might be a beneficial strategy for PH treatment. | ||
| 650 | 4 | |a Pulmonary hypertension |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a PPARγ |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a TRPC |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Hif-1α |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Lu, Wenju |4 aut | |
| 700 | 1 | |a Yang, Kai |4 aut | |
| 700 | 1 | |a Wang, Yan |4 aut | |
| 700 | 1 | |a Zhang, Jie |4 aut | |
| 700 | 1 | |a Jia, Jing |4 aut | |
| 700 | 1 | |a Yun, Xin |4 aut | |
| 700 | 1 | |a Tian, Lichun |4 aut | |
| 700 | 1 | |a Chen, Yuqin |4 aut | |
| 700 | 1 | |a Jiang, Qian |4 aut | |
| 700 | 1 | |a Zhang, Bo |4 aut | |
| 700 | 1 | |a Chen, Xiuqing |4 aut | |
| 700 | 1 | |a Wang, Jian |4 aut | |
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10.1007/s00109-014-1216-4 doi (DE-627)SPR000767212 (SPR)s00109-014-1216-4-e DE-627 ger DE-627 rakwb eng Wang, Yingfeng verfasserin aut Peroxisome proliferator-activated receptor γ inhibits pulmonary hypertension targeting store-operated calcium entry 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2014 Abstract In this study, we investigated the role of peroxisome proliferator-activated receptor γ (PPARγ) on store-operated calcium entry (SOCE) and expression of the main store-operated calcium channel (SOCCs) components, canonical transient receptor potential (TRPC) in chronic hypoxia (CH)-induced pulmonary hypertension (CHPH) rat models. Small interfering RNA (siRNA) knockdown and adenoviral overexpression strategies were constructed for loss-of-function and gain-of-function experiments. PPARγ agonist rosiglitazone attenuates the pathogenesis of CHPH and suppresses Hif-1α, TRPC1, TRPC6 expression in the distal pulmonary arteries (PA), and SOCE in freshly isolated rat distal pulmonary arterial smooth muscle cells (PASMCs). By comprehensive use of knockdown and overexpression studies, and bioinformatical analysis of the TRPC gene promoter and luciferase reporter assay, we demonstrated that PPARγ exerts roles of anti-proliferation, anti-migration, and pro-apoptosis in PASMCs, likely by inhibiting the elevated SOCE and TRPC expression. These effects were inhibited under the conditions of hypoxia or Hif-1α accumulation. We also found that under hypoxia, accumulated Hif-1α protein acts as upstream of suppressed PPARγ level; however, targeted PPARγ rescue acts as negative feedback on suppressing Hif-1α level and Hif-1α mediated signaling pathway. PPARγ inhibits CHPH by targeting SOCE and TRPC via inhibiting Hif-1α expression and signaling transduction. Key messages Rosiglitazone protects PH by normalizing RVSP but not right ventricle hypotrophy.PPARγ inhibits PASMCs proliferation via targeting SOCE and TRPC by suppressing Hif-1α.PPARγ and Hif-1α share mutual inhibitory regulation in PASMCs.PPARγ restoration might be a beneficial strategy for PH treatment. Pulmonary hypertension (dpeaa)DE-He213 PPARγ (dpeaa)DE-He213 TRPC (dpeaa)DE-He213 Hif-1α (dpeaa)DE-He213 Lu, Wenju aut Yang, Kai aut Wang, Yan aut Zhang, Jie aut Jia, Jing aut Yun, Xin aut Tian, Lichun aut Chen, Yuqin aut Jiang, Qian aut Zhang, Bo aut Chen, Xiuqing aut Wang, Jian aut Enthalten in Journal of molecular medicine Berlin : Springer, 1922 93(2014), 3 vom: 14. Nov., Seite 327-342 (DE-627)254630804 (DE-600)1462132-0 1432-1440 nnns volume:93 year:2014 number:3 day:14 month:11 pages:327-342 https://dx.doi.org/10.1007/s00109-014-1216-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 93 2014 3 14 11 327-342 |
| spelling |
10.1007/s00109-014-1216-4 doi (DE-627)SPR000767212 (SPR)s00109-014-1216-4-e DE-627 ger DE-627 rakwb eng Wang, Yingfeng verfasserin aut Peroxisome proliferator-activated receptor γ inhibits pulmonary hypertension targeting store-operated calcium entry 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2014 Abstract In this study, we investigated the role of peroxisome proliferator-activated receptor γ (PPARγ) on store-operated calcium entry (SOCE) and expression of the main store-operated calcium channel (SOCCs) components, canonical transient receptor potential (TRPC) in chronic hypoxia (CH)-induced pulmonary hypertension (CHPH) rat models. Small interfering RNA (siRNA) knockdown and adenoviral overexpression strategies were constructed for loss-of-function and gain-of-function experiments. PPARγ agonist rosiglitazone attenuates the pathogenesis of CHPH and suppresses Hif-1α, TRPC1, TRPC6 expression in the distal pulmonary arteries (PA), and SOCE in freshly isolated rat distal pulmonary arterial smooth muscle cells (PASMCs). By comprehensive use of knockdown and overexpression studies, and bioinformatical analysis of the TRPC gene promoter and luciferase reporter assay, we demonstrated that PPARγ exerts roles of anti-proliferation, anti-migration, and pro-apoptosis in PASMCs, likely by inhibiting the elevated SOCE and TRPC expression. These effects were inhibited under the conditions of hypoxia or Hif-1α accumulation. We also found that under hypoxia, accumulated Hif-1α protein acts as upstream of suppressed PPARγ level; however, targeted PPARγ rescue acts as negative feedback on suppressing Hif-1α level and Hif-1α mediated signaling pathway. PPARγ inhibits CHPH by targeting SOCE and TRPC via inhibiting Hif-1α expression and signaling transduction. Key messages Rosiglitazone protects PH by normalizing RVSP but not right ventricle hypotrophy.PPARγ inhibits PASMCs proliferation via targeting SOCE and TRPC by suppressing Hif-1α.PPARγ and Hif-1α share mutual inhibitory regulation in PASMCs.PPARγ restoration might be a beneficial strategy for PH treatment. Pulmonary hypertension (dpeaa)DE-He213 PPARγ (dpeaa)DE-He213 TRPC (dpeaa)DE-He213 Hif-1α (dpeaa)DE-He213 Lu, Wenju aut Yang, Kai aut Wang, Yan aut Zhang, Jie aut Jia, Jing aut Yun, Xin aut Tian, Lichun aut Chen, Yuqin aut Jiang, Qian aut Zhang, Bo aut Chen, Xiuqing aut Wang, Jian aut Enthalten in Journal of molecular medicine Berlin : Springer, 1922 93(2014), 3 vom: 14. Nov., Seite 327-342 (DE-627)254630804 (DE-600)1462132-0 1432-1440 nnns volume:93 year:2014 number:3 day:14 month:11 pages:327-342 https://dx.doi.org/10.1007/s00109-014-1216-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 93 2014 3 14 11 327-342 |
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10.1007/s00109-014-1216-4 doi (DE-627)SPR000767212 (SPR)s00109-014-1216-4-e DE-627 ger DE-627 rakwb eng Wang, Yingfeng verfasserin aut Peroxisome proliferator-activated receptor γ inhibits pulmonary hypertension targeting store-operated calcium entry 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2014 Abstract In this study, we investigated the role of peroxisome proliferator-activated receptor γ (PPARγ) on store-operated calcium entry (SOCE) and expression of the main store-operated calcium channel (SOCCs) components, canonical transient receptor potential (TRPC) in chronic hypoxia (CH)-induced pulmonary hypertension (CHPH) rat models. Small interfering RNA (siRNA) knockdown and adenoviral overexpression strategies were constructed for loss-of-function and gain-of-function experiments. PPARγ agonist rosiglitazone attenuates the pathogenesis of CHPH and suppresses Hif-1α, TRPC1, TRPC6 expression in the distal pulmonary arteries (PA), and SOCE in freshly isolated rat distal pulmonary arterial smooth muscle cells (PASMCs). By comprehensive use of knockdown and overexpression studies, and bioinformatical analysis of the TRPC gene promoter and luciferase reporter assay, we demonstrated that PPARγ exerts roles of anti-proliferation, anti-migration, and pro-apoptosis in PASMCs, likely by inhibiting the elevated SOCE and TRPC expression. These effects were inhibited under the conditions of hypoxia or Hif-1α accumulation. We also found that under hypoxia, accumulated Hif-1α protein acts as upstream of suppressed PPARγ level; however, targeted PPARγ rescue acts as negative feedback on suppressing Hif-1α level and Hif-1α mediated signaling pathway. PPARγ inhibits CHPH by targeting SOCE and TRPC via inhibiting Hif-1α expression and signaling transduction. Key messages Rosiglitazone protects PH by normalizing RVSP but not right ventricle hypotrophy.PPARγ inhibits PASMCs proliferation via targeting SOCE and TRPC by suppressing Hif-1α.PPARγ and Hif-1α share mutual inhibitory regulation in PASMCs.PPARγ restoration might be a beneficial strategy for PH treatment. Pulmonary hypertension (dpeaa)DE-He213 PPARγ (dpeaa)DE-He213 TRPC (dpeaa)DE-He213 Hif-1α (dpeaa)DE-He213 Lu, Wenju aut Yang, Kai aut Wang, Yan aut Zhang, Jie aut Jia, Jing aut Yun, Xin aut Tian, Lichun aut Chen, Yuqin aut Jiang, Qian aut Zhang, Bo aut Chen, Xiuqing aut Wang, Jian aut Enthalten in Journal of molecular medicine Berlin : Springer, 1922 93(2014), 3 vom: 14. Nov., Seite 327-342 (DE-627)254630804 (DE-600)1462132-0 1432-1440 nnns volume:93 year:2014 number:3 day:14 month:11 pages:327-342 https://dx.doi.org/10.1007/s00109-014-1216-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 93 2014 3 14 11 327-342 |
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10.1007/s00109-014-1216-4 doi (DE-627)SPR000767212 (SPR)s00109-014-1216-4-e DE-627 ger DE-627 rakwb eng Wang, Yingfeng verfasserin aut Peroxisome proliferator-activated receptor γ inhibits pulmonary hypertension targeting store-operated calcium entry 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2014 Abstract In this study, we investigated the role of peroxisome proliferator-activated receptor γ (PPARγ) on store-operated calcium entry (SOCE) and expression of the main store-operated calcium channel (SOCCs) components, canonical transient receptor potential (TRPC) in chronic hypoxia (CH)-induced pulmonary hypertension (CHPH) rat models. Small interfering RNA (siRNA) knockdown and adenoviral overexpression strategies were constructed for loss-of-function and gain-of-function experiments. PPARγ agonist rosiglitazone attenuates the pathogenesis of CHPH and suppresses Hif-1α, TRPC1, TRPC6 expression in the distal pulmonary arteries (PA), and SOCE in freshly isolated rat distal pulmonary arterial smooth muscle cells (PASMCs). By comprehensive use of knockdown and overexpression studies, and bioinformatical analysis of the TRPC gene promoter and luciferase reporter assay, we demonstrated that PPARγ exerts roles of anti-proliferation, anti-migration, and pro-apoptosis in PASMCs, likely by inhibiting the elevated SOCE and TRPC expression. These effects were inhibited under the conditions of hypoxia or Hif-1α accumulation. We also found that under hypoxia, accumulated Hif-1α protein acts as upstream of suppressed PPARγ level; however, targeted PPARγ rescue acts as negative feedback on suppressing Hif-1α level and Hif-1α mediated signaling pathway. PPARγ inhibits CHPH by targeting SOCE and TRPC via inhibiting Hif-1α expression and signaling transduction. Key messages Rosiglitazone protects PH by normalizing RVSP but not right ventricle hypotrophy.PPARγ inhibits PASMCs proliferation via targeting SOCE and TRPC by suppressing Hif-1α.PPARγ and Hif-1α share mutual inhibitory regulation in PASMCs.PPARγ restoration might be a beneficial strategy for PH treatment. Pulmonary hypertension (dpeaa)DE-He213 PPARγ (dpeaa)DE-He213 TRPC (dpeaa)DE-He213 Hif-1α (dpeaa)DE-He213 Lu, Wenju aut Yang, Kai aut Wang, Yan aut Zhang, Jie aut Jia, Jing aut Yun, Xin aut Tian, Lichun aut Chen, Yuqin aut Jiang, Qian aut Zhang, Bo aut Chen, Xiuqing aut Wang, Jian aut Enthalten in Journal of molecular medicine Berlin : Springer, 1922 93(2014), 3 vom: 14. Nov., Seite 327-342 (DE-627)254630804 (DE-600)1462132-0 1432-1440 nnns volume:93 year:2014 number:3 day:14 month:11 pages:327-342 https://dx.doi.org/10.1007/s00109-014-1216-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 93 2014 3 14 11 327-342 |
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10.1007/s00109-014-1216-4 doi (DE-627)SPR000767212 (SPR)s00109-014-1216-4-e DE-627 ger DE-627 rakwb eng Wang, Yingfeng verfasserin aut Peroxisome proliferator-activated receptor γ inhibits pulmonary hypertension targeting store-operated calcium entry 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Springer-Verlag Berlin Heidelberg 2014 Abstract In this study, we investigated the role of peroxisome proliferator-activated receptor γ (PPARγ) on store-operated calcium entry (SOCE) and expression of the main store-operated calcium channel (SOCCs) components, canonical transient receptor potential (TRPC) in chronic hypoxia (CH)-induced pulmonary hypertension (CHPH) rat models. Small interfering RNA (siRNA) knockdown and adenoviral overexpression strategies were constructed for loss-of-function and gain-of-function experiments. PPARγ agonist rosiglitazone attenuates the pathogenesis of CHPH and suppresses Hif-1α, TRPC1, TRPC6 expression in the distal pulmonary arteries (PA), and SOCE in freshly isolated rat distal pulmonary arterial smooth muscle cells (PASMCs). By comprehensive use of knockdown and overexpression studies, and bioinformatical analysis of the TRPC gene promoter and luciferase reporter assay, we demonstrated that PPARγ exerts roles of anti-proliferation, anti-migration, and pro-apoptosis in PASMCs, likely by inhibiting the elevated SOCE and TRPC expression. These effects were inhibited under the conditions of hypoxia or Hif-1α accumulation. We also found that under hypoxia, accumulated Hif-1α protein acts as upstream of suppressed PPARγ level; however, targeted PPARγ rescue acts as negative feedback on suppressing Hif-1α level and Hif-1α mediated signaling pathway. PPARγ inhibits CHPH by targeting SOCE and TRPC via inhibiting Hif-1α expression and signaling transduction. Key messages Rosiglitazone protects PH by normalizing RVSP but not right ventricle hypotrophy.PPARγ inhibits PASMCs proliferation via targeting SOCE and TRPC by suppressing Hif-1α.PPARγ and Hif-1α share mutual inhibitory regulation in PASMCs.PPARγ restoration might be a beneficial strategy for PH treatment. Pulmonary hypertension (dpeaa)DE-He213 PPARγ (dpeaa)DE-He213 TRPC (dpeaa)DE-He213 Hif-1α (dpeaa)DE-He213 Lu, Wenju aut Yang, Kai aut Wang, Yan aut Zhang, Jie aut Jia, Jing aut Yun, Xin aut Tian, Lichun aut Chen, Yuqin aut Jiang, Qian aut Zhang, Bo aut Chen, Xiuqing aut Wang, Jian aut Enthalten in Journal of molecular medicine Berlin : Springer, 1922 93(2014), 3 vom: 14. Nov., Seite 327-342 (DE-627)254630804 (DE-600)1462132-0 1432-1440 nnns volume:93 year:2014 number:3 day:14 month:11 pages:327-342 https://dx.doi.org/10.1007/s00109-014-1216-4 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_267 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2070 GBV_ILN_2086 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2116 GBV_ILN_2118 GBV_ILN_2119 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 93 2014 3 14 11 327-342 |
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Enthalten in Journal of molecular medicine 93(2014), 3 vom: 14. Nov., Seite 327-342 volume:93 year:2014 number:3 day:14 month:11 pages:327-342 |
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Enthalten in Journal of molecular medicine 93(2014), 3 vom: 14. Nov., Seite 327-342 volume:93 year:2014 number:3 day:14 month:11 pages:327-342 |
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Pulmonary hypertension PPARγ TRPC Hif-1α |
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Wang, Yingfeng @@aut@@ Lu, Wenju @@aut@@ Yang, Kai @@aut@@ Wang, Yan @@aut@@ Zhang, Jie @@aut@@ Jia, Jing @@aut@@ Yun, Xin @@aut@@ Tian, Lichun @@aut@@ Chen, Yuqin @@aut@@ Jiang, Qian @@aut@@ Zhang, Bo @@aut@@ Chen, Xiuqing @@aut@@ Wang, Jian @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR000767212</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519160237.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201001s2014 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s00109-014-1216-4</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR000767212</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s00109-014-1216-4-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Wang, Yingfeng</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Peroxisome proliferator-activated receptor γ inhibits pulmonary hypertension targeting store-operated calcium entry</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2014</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© Springer-Verlag Berlin Heidelberg 2014</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Abstract In this study, we investigated the role of peroxisome proliferator-activated receptor γ (PPARγ) on store-operated calcium entry (SOCE) and expression of the main store-operated calcium channel (SOCCs) components, canonical transient receptor potential (TRPC) in chronic hypoxia (CH)-induced pulmonary hypertension (CHPH) rat models. Small interfering RNA (siRNA) knockdown and adenoviral overexpression strategies were constructed for loss-of-function and gain-of-function experiments. PPARγ agonist rosiglitazone attenuates the pathogenesis of CHPH and suppresses Hif-1α, TRPC1, TRPC6 expression in the distal pulmonary arteries (PA), and SOCE in freshly isolated rat distal pulmonary arterial smooth muscle cells (PASMCs). By comprehensive use of knockdown and overexpression studies, and bioinformatical analysis of the TRPC gene promoter and luciferase reporter assay, we demonstrated that PPARγ exerts roles of anti-proliferation, anti-migration, and pro-apoptosis in PASMCs, likely by inhibiting the elevated SOCE and TRPC expression. These effects were inhibited under the conditions of hypoxia or Hif-1α accumulation. We also found that under hypoxia, accumulated Hif-1α protein acts as upstream of suppressed PPARγ level; however, targeted PPARγ rescue acts as negative feedback on suppressing Hif-1α level and Hif-1α mediated signaling pathway. PPARγ inhibits CHPH by targeting SOCE and TRPC via inhibiting Hif-1α expression and signaling transduction. Key messages Rosiglitazone protects PH by normalizing RVSP but not right ventricle hypotrophy.PPARγ inhibits PASMCs proliferation via targeting SOCE and TRPC by suppressing Hif-1α.PPARγ and Hif-1α share mutual inhibitory regulation in PASMCs.PPARγ restoration might be a beneficial strategy for PH treatment.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Pulmonary hypertension</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">PPARγ</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">TRPC</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Hif-1α</subfield><subfield code="7">(dpeaa)DE-He213</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Lu, Wenju</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yang, Kai</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wang, Yan</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhang, Jie</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Jia, Jing</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Yun, Xin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tian, Lichun</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Chen, Yuqin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Jiang, Qian</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Zhang, Bo</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Chen, Xiuqing</subfield><subfield code="4">aut</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wang, Jian</subfield><subfield code="4">aut</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="t">Journal of molecular medicine</subfield><subfield code="d">Berlin : Springer, 1922</subfield><subfield code="g">93(2014), 3 vom: 14. 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Wang, Yingfeng |
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Wang, Yingfeng misc Pulmonary hypertension misc PPARγ misc TRPC misc Hif-1α Peroxisome proliferator-activated receptor γ inhibits pulmonary hypertension targeting store-operated calcium entry |
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Peroxisome proliferator-activated receptor γ inhibits pulmonary hypertension targeting store-operated calcium entry Pulmonary hypertension (dpeaa)DE-He213 PPARγ (dpeaa)DE-He213 TRPC (dpeaa)DE-He213 Hif-1α (dpeaa)DE-He213 |
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Wang, Yingfeng Lu, Wenju Yang, Kai Wang, Yan Zhang, Jie Jia, Jing Yun, Xin Tian, Lichun Chen, Yuqin Jiang, Qian Zhang, Bo Chen, Xiuqing Wang, Jian |
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Elektronische Aufsätze |
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Wang, Yingfeng |
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10.1007/s00109-014-1216-4 |
| title_sort |
peroxisome proliferator-activated receptor γ inhibits pulmonary hypertension targeting store-operated calcium entry |
| title_auth |
Peroxisome proliferator-activated receptor γ inhibits pulmonary hypertension targeting store-operated calcium entry |
| abstract |
Abstract In this study, we investigated the role of peroxisome proliferator-activated receptor γ (PPARγ) on store-operated calcium entry (SOCE) and expression of the main store-operated calcium channel (SOCCs) components, canonical transient receptor potential (TRPC) in chronic hypoxia (CH)-induced pulmonary hypertension (CHPH) rat models. Small interfering RNA (siRNA) knockdown and adenoviral overexpression strategies were constructed for loss-of-function and gain-of-function experiments. PPARγ agonist rosiglitazone attenuates the pathogenesis of CHPH and suppresses Hif-1α, TRPC1, TRPC6 expression in the distal pulmonary arteries (PA), and SOCE in freshly isolated rat distal pulmonary arterial smooth muscle cells (PASMCs). By comprehensive use of knockdown and overexpression studies, and bioinformatical analysis of the TRPC gene promoter and luciferase reporter assay, we demonstrated that PPARγ exerts roles of anti-proliferation, anti-migration, and pro-apoptosis in PASMCs, likely by inhibiting the elevated SOCE and TRPC expression. These effects were inhibited under the conditions of hypoxia or Hif-1α accumulation. We also found that under hypoxia, accumulated Hif-1α protein acts as upstream of suppressed PPARγ level; however, targeted PPARγ rescue acts as negative feedback on suppressing Hif-1α level and Hif-1α mediated signaling pathway. PPARγ inhibits CHPH by targeting SOCE and TRPC via inhibiting Hif-1α expression and signaling transduction. Key messages Rosiglitazone protects PH by normalizing RVSP but not right ventricle hypotrophy.PPARγ inhibits PASMCs proliferation via targeting SOCE and TRPC by suppressing Hif-1α.PPARγ and Hif-1α share mutual inhibitory regulation in PASMCs.PPARγ restoration might be a beneficial strategy for PH treatment. © Springer-Verlag Berlin Heidelberg 2014 |
| abstractGer |
Abstract In this study, we investigated the role of peroxisome proliferator-activated receptor γ (PPARγ) on store-operated calcium entry (SOCE) and expression of the main store-operated calcium channel (SOCCs) components, canonical transient receptor potential (TRPC) in chronic hypoxia (CH)-induced pulmonary hypertension (CHPH) rat models. Small interfering RNA (siRNA) knockdown and adenoviral overexpression strategies were constructed for loss-of-function and gain-of-function experiments. PPARγ agonist rosiglitazone attenuates the pathogenesis of CHPH and suppresses Hif-1α, TRPC1, TRPC6 expression in the distal pulmonary arteries (PA), and SOCE in freshly isolated rat distal pulmonary arterial smooth muscle cells (PASMCs). By comprehensive use of knockdown and overexpression studies, and bioinformatical analysis of the TRPC gene promoter and luciferase reporter assay, we demonstrated that PPARγ exerts roles of anti-proliferation, anti-migration, and pro-apoptosis in PASMCs, likely by inhibiting the elevated SOCE and TRPC expression. These effects were inhibited under the conditions of hypoxia or Hif-1α accumulation. We also found that under hypoxia, accumulated Hif-1α protein acts as upstream of suppressed PPARγ level; however, targeted PPARγ rescue acts as negative feedback on suppressing Hif-1α level and Hif-1α mediated signaling pathway. PPARγ inhibits CHPH by targeting SOCE and TRPC via inhibiting Hif-1α expression and signaling transduction. Key messages Rosiglitazone protects PH by normalizing RVSP but not right ventricle hypotrophy.PPARγ inhibits PASMCs proliferation via targeting SOCE and TRPC by suppressing Hif-1α.PPARγ and Hif-1α share mutual inhibitory regulation in PASMCs.PPARγ restoration might be a beneficial strategy for PH treatment. © Springer-Verlag Berlin Heidelberg 2014 |
| abstract_unstemmed |
Abstract In this study, we investigated the role of peroxisome proliferator-activated receptor γ (PPARγ) on store-operated calcium entry (SOCE) and expression of the main store-operated calcium channel (SOCCs) components, canonical transient receptor potential (TRPC) in chronic hypoxia (CH)-induced pulmonary hypertension (CHPH) rat models. Small interfering RNA (siRNA) knockdown and adenoviral overexpression strategies were constructed for loss-of-function and gain-of-function experiments. PPARγ agonist rosiglitazone attenuates the pathogenesis of CHPH and suppresses Hif-1α, TRPC1, TRPC6 expression in the distal pulmonary arteries (PA), and SOCE in freshly isolated rat distal pulmonary arterial smooth muscle cells (PASMCs). By comprehensive use of knockdown and overexpression studies, and bioinformatical analysis of the TRPC gene promoter and luciferase reporter assay, we demonstrated that PPARγ exerts roles of anti-proliferation, anti-migration, and pro-apoptosis in PASMCs, likely by inhibiting the elevated SOCE and TRPC expression. These effects were inhibited under the conditions of hypoxia or Hif-1α accumulation. We also found that under hypoxia, accumulated Hif-1α protein acts as upstream of suppressed PPARγ level; however, targeted PPARγ rescue acts as negative feedback on suppressing Hif-1α level and Hif-1α mediated signaling pathway. PPARγ inhibits CHPH by targeting SOCE and TRPC via inhibiting Hif-1α expression and signaling transduction. Key messages Rosiglitazone protects PH by normalizing RVSP but not right ventricle hypotrophy.PPARγ inhibits PASMCs proliferation via targeting SOCE and TRPC by suppressing Hif-1α.PPARγ and Hif-1α share mutual inhibitory regulation in PASMCs.PPARγ restoration might be a beneficial strategy for PH treatment. © Springer-Verlag Berlin Heidelberg 2014 |
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Peroxisome proliferator-activated receptor γ inhibits pulmonary hypertension targeting store-operated calcium entry |
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Lu, Wenju Yang, Kai Wang, Yan Zhang, Jie Jia, Jing Yun, Xin Tian, Lichun Chen, Yuqin Jiang, Qian Zhang, Bo Chen, Xiuqing Wang, Jian |
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Lu, Wenju Yang, Kai Wang, Yan Zhang, Jie Jia, Jing Yun, Xin Tian, Lichun Chen, Yuqin Jiang, Qian Zhang, Bo Chen, Xiuqing Wang, Jian |
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| score |
7.3986425 |