Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis Through the TNFR1-NF-κB/MAPKs Pathway
Background Ulcerative colitis (UC) is an idiopathic colonic mucosal disease, and its pathogenesis has not been fully understood. Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. Aim The present study aimed to validate the underlying mechanism of UP...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Zhu, Huatuo [verfasserIn] Huang, Shujun [verfasserIn] Yue, Min [verfasserIn] Chen, Wenguo [verfasserIn] Lu, Chao [verfasserIn] Lou, Xinhe [verfasserIn] Li, Chunxiao [verfasserIn] Shan, Guodong [verfasserIn] Chen, Hongtan [verfasserIn] Xu, Xiaowei [verfasserIn] Xu, Guoqiang [verfasserIn] Chen, Lihua [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2018 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Digestive diseases and sciences - Dordrecht : Springer Science + Business Media B.V., 1934, 63(2018), 10 vom: 29. Juni, Seite 2593-2603 |
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| Übergeordnetes Werk: |
volume:63 ; year:2018 ; number:10 ; day:29 ; month:06 ; pages:2593-2603 |
| Links: |
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| DOI / URN: |
10.1007/s10620-018-5171-8 |
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| Katalog-ID: |
SPR011893028 |
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| 245 | 1 | 0 | |a Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis Through the TNFR1-NF-κB/MAPKs Pathway |
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| 520 | |a Background Ulcerative colitis (UC) is an idiopathic colonic mucosal disease, and its pathogenesis has not been fully understood. Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. Aim The present study aimed to validate the underlying mechanism of UPF1 in UC. Methods UPF1 expression was detected by qRT-PCR, western blotting, and immunohistochemistry in dextran sulfate sodium-induced colitis in mice. To simulate the intestinal inflammation microenvironment, NCM460 human colonic epithelial cells were exposed to a mixture of inflammatory mediators. The potential mechanism involving TNFR1-NF-κB/MAPKs pathway activation was addressed by western blotting, reporter gene assays, and siRNA (siUPF1) or UPF1-expressing plasmid pENTER-transfected cells. Results UPF1 was downregulated in colonic epithelial cells of colitic mice, and in vitro, contrary to the mRNA levels of the associated cytokines enhanced in the UPF1 dysregulation group within stimulatory factors, most relevant cytokines were significantly decreased in UPF1 overexpression group. Mechanistically, the increased expression of tumor necrosis factor receptor 1 (TNFR1) was found in NCM460 cells pre-treated with siUPF1, with the activation of IKK/NF-κB and MAPKs pathways, including JNK/AP-1 and P38, but not the ERK1/2 pathway. Moreover, the repression of TNFR1 required the interaction of UPF1 with the promoter. Conclusion UPF1, which negatively regulated the transcription of TNFR1, is a novel factor regulating intestinal inflammation. The downregulation of UPF1 activated the TNFR1-dependent NF-κB/MAPKs pathway, and promoting inflammatory responses in colon might act as a causal role in UC. | ||
| 650 | 4 | |a Ulcerative colitis (UC) |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Up-frameshift mutant 1 (UPF1) |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Tumor necrosis factor receptor 1 (TNFR1) |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a NF-κB/MAPKs pathway |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Huang, Shujun |e verfasserin |4 aut | |
| 700 | 1 | |a Yue, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Wenguo |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Lou, Xinhe |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Chunxiao |e verfasserin |4 aut | |
| 700 | 1 | |a Shan, Guodong |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Hongtan |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Xiaowei |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Guoqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Lihua |e verfasserin |4 aut | |
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10.1007/s10620-018-5171-8 doi (DE-627)SPR011893028 (SPR)s10620-018-5171-8-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.87 bkl Zhu, Huatuo verfasserin aut Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis Through the TNFR1-NF-κB/MAPKs Pathway 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Ulcerative colitis (UC) is an idiopathic colonic mucosal disease, and its pathogenesis has not been fully understood. Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. Aim The present study aimed to validate the underlying mechanism of UPF1 in UC. Methods UPF1 expression was detected by qRT-PCR, western blotting, and immunohistochemistry in dextran sulfate sodium-induced colitis in mice. To simulate the intestinal inflammation microenvironment, NCM460 human colonic epithelial cells were exposed to a mixture of inflammatory mediators. The potential mechanism involving TNFR1-NF-κB/MAPKs pathway activation was addressed by western blotting, reporter gene assays, and siRNA (siUPF1) or UPF1-expressing plasmid pENTER-transfected cells. Results UPF1 was downregulated in colonic epithelial cells of colitic mice, and in vitro, contrary to the mRNA levels of the associated cytokines enhanced in the UPF1 dysregulation group within stimulatory factors, most relevant cytokines were significantly decreased in UPF1 overexpression group. Mechanistically, the increased expression of tumor necrosis factor receptor 1 (TNFR1) was found in NCM460 cells pre-treated with siUPF1, with the activation of IKK/NF-κB and MAPKs pathways, including JNK/AP-1 and P38, but not the ERK1/2 pathway. Moreover, the repression of TNFR1 required the interaction of UPF1 with the promoter. Conclusion UPF1, which negatively regulated the transcription of TNFR1, is a novel factor regulating intestinal inflammation. The downregulation of UPF1 activated the TNFR1-dependent NF-κB/MAPKs pathway, and promoting inflammatory responses in colon might act as a causal role in UC. Ulcerative colitis (UC) (dpeaa)DE-He213 Up-frameshift mutant 1 (UPF1) (dpeaa)DE-He213 Tumor necrosis factor receptor 1 (TNFR1) (dpeaa)DE-He213 NF-κB/MAPKs pathway (dpeaa)DE-He213 Huang, Shujun verfasserin aut Yue, Min verfasserin aut Chen, Wenguo verfasserin aut Lu, Chao verfasserin aut Lou, Xinhe verfasserin aut Li, Chunxiao verfasserin aut Shan, Guodong verfasserin aut Chen, Hongtan verfasserin aut Xu, Xiaowei verfasserin aut Xu, Guoqiang verfasserin aut Chen, Lihua verfasserin aut Enthalten in Digestive diseases and sciences Dordrecht : Springer Science + Business Media B.V., 1934 63(2018), 10 vom: 29. Juni, Seite 2593-2603 (DE-627)320525384 (DE-600)2015102-0 1573-2568 nnns volume:63 year:2018 number:10 day:29 month:06 pages:2593-2603 https://dx.doi.org/10.1007/s10620-018-5171-8 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_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_711 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_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.87 ASE AR 63 2018 10 29 06 2593-2603 |
| spelling |
10.1007/s10620-018-5171-8 doi (DE-627)SPR011893028 (SPR)s10620-018-5171-8-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.87 bkl Zhu, Huatuo verfasserin aut Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis Through the TNFR1-NF-κB/MAPKs Pathway 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Ulcerative colitis (UC) is an idiopathic colonic mucosal disease, and its pathogenesis has not been fully understood. Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. Aim The present study aimed to validate the underlying mechanism of UPF1 in UC. Methods UPF1 expression was detected by qRT-PCR, western blotting, and immunohistochemistry in dextran sulfate sodium-induced colitis in mice. To simulate the intestinal inflammation microenvironment, NCM460 human colonic epithelial cells were exposed to a mixture of inflammatory mediators. The potential mechanism involving TNFR1-NF-κB/MAPKs pathway activation was addressed by western blotting, reporter gene assays, and siRNA (siUPF1) or UPF1-expressing plasmid pENTER-transfected cells. Results UPF1 was downregulated in colonic epithelial cells of colitic mice, and in vitro, contrary to the mRNA levels of the associated cytokines enhanced in the UPF1 dysregulation group within stimulatory factors, most relevant cytokines were significantly decreased in UPF1 overexpression group. Mechanistically, the increased expression of tumor necrosis factor receptor 1 (TNFR1) was found in NCM460 cells pre-treated with siUPF1, with the activation of IKK/NF-κB and MAPKs pathways, including JNK/AP-1 and P38, but not the ERK1/2 pathway. Moreover, the repression of TNFR1 required the interaction of UPF1 with the promoter. Conclusion UPF1, which negatively regulated the transcription of TNFR1, is a novel factor regulating intestinal inflammation. The downregulation of UPF1 activated the TNFR1-dependent NF-κB/MAPKs pathway, and promoting inflammatory responses in colon might act as a causal role in UC. Ulcerative colitis (UC) (dpeaa)DE-He213 Up-frameshift mutant 1 (UPF1) (dpeaa)DE-He213 Tumor necrosis factor receptor 1 (TNFR1) (dpeaa)DE-He213 NF-κB/MAPKs pathway (dpeaa)DE-He213 Huang, Shujun verfasserin aut Yue, Min verfasserin aut Chen, Wenguo verfasserin aut Lu, Chao verfasserin aut Lou, Xinhe verfasserin aut Li, Chunxiao verfasserin aut Shan, Guodong verfasserin aut Chen, Hongtan verfasserin aut Xu, Xiaowei verfasserin aut Xu, Guoqiang verfasserin aut Chen, Lihua verfasserin aut Enthalten in Digestive diseases and sciences Dordrecht : Springer Science + Business Media B.V., 1934 63(2018), 10 vom: 29. Juni, Seite 2593-2603 (DE-627)320525384 (DE-600)2015102-0 1573-2568 nnns volume:63 year:2018 number:10 day:29 month:06 pages:2593-2603 https://dx.doi.org/10.1007/s10620-018-5171-8 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_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_711 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_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.87 ASE AR 63 2018 10 29 06 2593-2603 |
| allfields_unstemmed |
10.1007/s10620-018-5171-8 doi (DE-627)SPR011893028 (SPR)s10620-018-5171-8-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.87 bkl Zhu, Huatuo verfasserin aut Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis Through the TNFR1-NF-κB/MAPKs Pathway 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Ulcerative colitis (UC) is an idiopathic colonic mucosal disease, and its pathogenesis has not been fully understood. Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. Aim The present study aimed to validate the underlying mechanism of UPF1 in UC. Methods UPF1 expression was detected by qRT-PCR, western blotting, and immunohistochemistry in dextran sulfate sodium-induced colitis in mice. To simulate the intestinal inflammation microenvironment, NCM460 human colonic epithelial cells were exposed to a mixture of inflammatory mediators. The potential mechanism involving TNFR1-NF-κB/MAPKs pathway activation was addressed by western blotting, reporter gene assays, and siRNA (siUPF1) or UPF1-expressing plasmid pENTER-transfected cells. Results UPF1 was downregulated in colonic epithelial cells of colitic mice, and in vitro, contrary to the mRNA levels of the associated cytokines enhanced in the UPF1 dysregulation group within stimulatory factors, most relevant cytokines were significantly decreased in UPF1 overexpression group. Mechanistically, the increased expression of tumor necrosis factor receptor 1 (TNFR1) was found in NCM460 cells pre-treated with siUPF1, with the activation of IKK/NF-κB and MAPKs pathways, including JNK/AP-1 and P38, but not the ERK1/2 pathway. Moreover, the repression of TNFR1 required the interaction of UPF1 with the promoter. Conclusion UPF1, which negatively regulated the transcription of TNFR1, is a novel factor regulating intestinal inflammation. The downregulation of UPF1 activated the TNFR1-dependent NF-κB/MAPKs pathway, and promoting inflammatory responses in colon might act as a causal role in UC. Ulcerative colitis (UC) (dpeaa)DE-He213 Up-frameshift mutant 1 (UPF1) (dpeaa)DE-He213 Tumor necrosis factor receptor 1 (TNFR1) (dpeaa)DE-He213 NF-κB/MAPKs pathway (dpeaa)DE-He213 Huang, Shujun verfasserin aut Yue, Min verfasserin aut Chen, Wenguo verfasserin aut Lu, Chao verfasserin aut Lou, Xinhe verfasserin aut Li, Chunxiao verfasserin aut Shan, Guodong verfasserin aut Chen, Hongtan verfasserin aut Xu, Xiaowei verfasserin aut Xu, Guoqiang verfasserin aut Chen, Lihua verfasserin aut Enthalten in Digestive diseases and sciences Dordrecht : Springer Science + Business Media B.V., 1934 63(2018), 10 vom: 29. Juni, Seite 2593-2603 (DE-627)320525384 (DE-600)2015102-0 1573-2568 nnns volume:63 year:2018 number:10 day:29 month:06 pages:2593-2603 https://dx.doi.org/10.1007/s10620-018-5171-8 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_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_711 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_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.87 ASE AR 63 2018 10 29 06 2593-2603 |
| allfieldsGer |
10.1007/s10620-018-5171-8 doi (DE-627)SPR011893028 (SPR)s10620-018-5171-8-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.87 bkl Zhu, Huatuo verfasserin aut Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis Through the TNFR1-NF-κB/MAPKs Pathway 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Ulcerative colitis (UC) is an idiopathic colonic mucosal disease, and its pathogenesis has not been fully understood. Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. Aim The present study aimed to validate the underlying mechanism of UPF1 in UC. Methods UPF1 expression was detected by qRT-PCR, western blotting, and immunohistochemistry in dextran sulfate sodium-induced colitis in mice. To simulate the intestinal inflammation microenvironment, NCM460 human colonic epithelial cells were exposed to a mixture of inflammatory mediators. The potential mechanism involving TNFR1-NF-κB/MAPKs pathway activation was addressed by western blotting, reporter gene assays, and siRNA (siUPF1) or UPF1-expressing plasmid pENTER-transfected cells. Results UPF1 was downregulated in colonic epithelial cells of colitic mice, and in vitro, contrary to the mRNA levels of the associated cytokines enhanced in the UPF1 dysregulation group within stimulatory factors, most relevant cytokines were significantly decreased in UPF1 overexpression group. Mechanistically, the increased expression of tumor necrosis factor receptor 1 (TNFR1) was found in NCM460 cells pre-treated with siUPF1, with the activation of IKK/NF-κB and MAPKs pathways, including JNK/AP-1 and P38, but not the ERK1/2 pathway. Moreover, the repression of TNFR1 required the interaction of UPF1 with the promoter. Conclusion UPF1, which negatively regulated the transcription of TNFR1, is a novel factor regulating intestinal inflammation. The downregulation of UPF1 activated the TNFR1-dependent NF-κB/MAPKs pathway, and promoting inflammatory responses in colon might act as a causal role in UC. Ulcerative colitis (UC) (dpeaa)DE-He213 Up-frameshift mutant 1 (UPF1) (dpeaa)DE-He213 Tumor necrosis factor receptor 1 (TNFR1) (dpeaa)DE-He213 NF-κB/MAPKs pathway (dpeaa)DE-He213 Huang, Shujun verfasserin aut Yue, Min verfasserin aut Chen, Wenguo verfasserin aut Lu, Chao verfasserin aut Lou, Xinhe verfasserin aut Li, Chunxiao verfasserin aut Shan, Guodong verfasserin aut Chen, Hongtan verfasserin aut Xu, Xiaowei verfasserin aut Xu, Guoqiang verfasserin aut Chen, Lihua verfasserin aut Enthalten in Digestive diseases and sciences Dordrecht : Springer Science + Business Media B.V., 1934 63(2018), 10 vom: 29. Juni, Seite 2593-2603 (DE-627)320525384 (DE-600)2015102-0 1573-2568 nnns volume:63 year:2018 number:10 day:29 month:06 pages:2593-2603 https://dx.doi.org/10.1007/s10620-018-5171-8 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_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_711 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_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.87 ASE AR 63 2018 10 29 06 2593-2603 |
| allfieldsSound |
10.1007/s10620-018-5171-8 doi (DE-627)SPR011893028 (SPR)s10620-018-5171-8-e DE-627 ger DE-627 rakwb eng 610 ASE 610 ASE 44.87 bkl Zhu, Huatuo verfasserin aut Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis Through the TNFR1-NF-κB/MAPKs Pathway 2018 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Background Ulcerative colitis (UC) is an idiopathic colonic mucosal disease, and its pathogenesis has not been fully understood. Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. Aim The present study aimed to validate the underlying mechanism of UPF1 in UC. Methods UPF1 expression was detected by qRT-PCR, western blotting, and immunohistochemistry in dextran sulfate sodium-induced colitis in mice. To simulate the intestinal inflammation microenvironment, NCM460 human colonic epithelial cells were exposed to a mixture of inflammatory mediators. The potential mechanism involving TNFR1-NF-κB/MAPKs pathway activation was addressed by western blotting, reporter gene assays, and siRNA (siUPF1) or UPF1-expressing plasmid pENTER-transfected cells. Results UPF1 was downregulated in colonic epithelial cells of colitic mice, and in vitro, contrary to the mRNA levels of the associated cytokines enhanced in the UPF1 dysregulation group within stimulatory factors, most relevant cytokines were significantly decreased in UPF1 overexpression group. Mechanistically, the increased expression of tumor necrosis factor receptor 1 (TNFR1) was found in NCM460 cells pre-treated with siUPF1, with the activation of IKK/NF-κB and MAPKs pathways, including JNK/AP-1 and P38, but not the ERK1/2 pathway. Moreover, the repression of TNFR1 required the interaction of UPF1 with the promoter. Conclusion UPF1, which negatively regulated the transcription of TNFR1, is a novel factor regulating intestinal inflammation. The downregulation of UPF1 activated the TNFR1-dependent NF-κB/MAPKs pathway, and promoting inflammatory responses in colon might act as a causal role in UC. Ulcerative colitis (UC) (dpeaa)DE-He213 Up-frameshift mutant 1 (UPF1) (dpeaa)DE-He213 Tumor necrosis factor receptor 1 (TNFR1) (dpeaa)DE-He213 NF-κB/MAPKs pathway (dpeaa)DE-He213 Huang, Shujun verfasserin aut Yue, Min verfasserin aut Chen, Wenguo verfasserin aut Lu, Chao verfasserin aut Lou, Xinhe verfasserin aut Li, Chunxiao verfasserin aut Shan, Guodong verfasserin aut Chen, Hongtan verfasserin aut Xu, Xiaowei verfasserin aut Xu, Guoqiang verfasserin aut Chen, Lihua verfasserin aut Enthalten in Digestive diseases and sciences Dordrecht : Springer Science + Business Media B.V., 1934 63(2018), 10 vom: 29. Juni, Seite 2593-2603 (DE-627)320525384 (DE-600)2015102-0 1573-2568 nnns volume:63 year:2018 number:10 day:29 month:06 pages:2593-2603 https://dx.doi.org/10.1007/s10620-018-5171-8 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_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_711 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_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.87 ASE AR 63 2018 10 29 06 2593-2603 |
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Enthalten in Digestive diseases and sciences 63(2018), 10 vom: 29. Juni, Seite 2593-2603 volume:63 year:2018 number:10 day:29 month:06 pages:2593-2603 |
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Ulcerative colitis (UC) Up-frameshift mutant 1 (UPF1) Tumor necrosis factor receptor 1 (TNFR1) NF-κB/MAPKs pathway |
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Zhu, Huatuo @@aut@@ Huang, Shujun @@aut@@ Yue, Min @@aut@@ Chen, Wenguo @@aut@@ Lu, Chao @@aut@@ Lou, Xinhe @@aut@@ Li, Chunxiao @@aut@@ Shan, Guodong @@aut@@ Chen, Hongtan @@aut@@ Xu, Xiaowei @@aut@@ Xu, Guoqiang @@aut@@ Chen, Lihua @@aut@@ |
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Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. Aim The present study aimed to validate the underlying mechanism of UPF1 in UC. Methods UPF1 expression was detected by qRT-PCR, western blotting, and immunohistochemistry in dextran sulfate sodium-induced colitis in mice. To simulate the intestinal inflammation microenvironment, NCM460 human colonic epithelial cells were exposed to a mixture of inflammatory mediators. The potential mechanism involving TNFR1-NF-κB/MAPKs pathway activation was addressed by western blotting, reporter gene assays, and siRNA (siUPF1) or UPF1-expressing plasmid pENTER-transfected cells. Results UPF1 was downregulated in colonic epithelial cells of colitic mice, and in vitro, contrary to the mRNA levels of the associated cytokines enhanced in the UPF1 dysregulation group within stimulatory factors, most relevant cytokines were significantly decreased in UPF1 overexpression group. 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|
| author |
Zhu, Huatuo |
| spellingShingle |
Zhu, Huatuo ddc 610 bkl 44.87 misc Ulcerative colitis (UC) misc Up-frameshift mutant 1 (UPF1) misc Tumor necrosis factor receptor 1 (TNFR1) misc NF-κB/MAPKs pathway Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis Through the TNFR1-NF-κB/MAPKs Pathway |
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Zhu, Huatuo |
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610 - Medicine & health |
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1573-2568 |
| topic_title |
610 ASE 44.87 bkl Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis Through the TNFR1-NF-κB/MAPKs Pathway Ulcerative colitis (UC) (dpeaa)DE-He213 Up-frameshift mutant 1 (UPF1) (dpeaa)DE-He213 Tumor necrosis factor receptor 1 (TNFR1) (dpeaa)DE-He213 NF-κB/MAPKs pathway (dpeaa)DE-He213 |
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ddc 610 bkl 44.87 misc Ulcerative colitis (UC) misc Up-frameshift mutant 1 (UPF1) misc Tumor necrosis factor receptor 1 (TNFR1) misc NF-κB/MAPKs pathway |
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ddc 610 bkl 44.87 misc Ulcerative colitis (UC) misc Up-frameshift mutant 1 (UPF1) misc Tumor necrosis factor receptor 1 (TNFR1) misc NF-κB/MAPKs pathway |
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ddc 610 bkl 44.87 misc Ulcerative colitis (UC) misc Up-frameshift mutant 1 (UPF1) misc Tumor necrosis factor receptor 1 (TNFR1) misc NF-κB/MAPKs pathway |
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Digestive diseases and sciences |
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610 - Medicine & health |
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Digestive diseases and sciences |
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(DE-627)320525384 (DE-600)2015102-0 |
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Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis Through the TNFR1-NF-κB/MAPKs Pathway |
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(DE-627)SPR011893028 (SPR)s10620-018-5171-8-e |
| title_full |
Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis Through the TNFR1-NF-κB/MAPKs Pathway |
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Zhu, Huatuo |
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Digestive diseases and sciences |
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Digestive diseases and sciences |
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600 - Technology |
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2018 |
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2593 |
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Zhu, Huatuo Huang, Shujun Yue, Min Chen, Wenguo Lu, Chao Lou, Xinhe Li, Chunxiao Shan, Guodong Chen, Hongtan Xu, Xiaowei Xu, Guoqiang Chen, Lihua |
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Zhu, Huatuo |
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10.1007/s10620-018-5171-8 |
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610 |
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verfasserin |
| title_sort |
dysregulated up-frameshift protein 1 promotes ulcerative colitis pathogenesis through the tnfr1-nf-κb/mapks pathway |
| title_auth |
Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis Through the TNFR1-NF-κB/MAPKs Pathway |
| abstract |
Background Ulcerative colitis (UC) is an idiopathic colonic mucosal disease, and its pathogenesis has not been fully understood. Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. Aim The present study aimed to validate the underlying mechanism of UPF1 in UC. Methods UPF1 expression was detected by qRT-PCR, western blotting, and immunohistochemistry in dextran sulfate sodium-induced colitis in mice. To simulate the intestinal inflammation microenvironment, NCM460 human colonic epithelial cells were exposed to a mixture of inflammatory mediators. The potential mechanism involving TNFR1-NF-κB/MAPKs pathway activation was addressed by western blotting, reporter gene assays, and siRNA (siUPF1) or UPF1-expressing plasmid pENTER-transfected cells. Results UPF1 was downregulated in colonic epithelial cells of colitic mice, and in vitro, contrary to the mRNA levels of the associated cytokines enhanced in the UPF1 dysregulation group within stimulatory factors, most relevant cytokines were significantly decreased in UPF1 overexpression group. Mechanistically, the increased expression of tumor necrosis factor receptor 1 (TNFR1) was found in NCM460 cells pre-treated with siUPF1, with the activation of IKK/NF-κB and MAPKs pathways, including JNK/AP-1 and P38, but not the ERK1/2 pathway. Moreover, the repression of TNFR1 required the interaction of UPF1 with the promoter. Conclusion UPF1, which negatively regulated the transcription of TNFR1, is a novel factor regulating intestinal inflammation. The downregulation of UPF1 activated the TNFR1-dependent NF-κB/MAPKs pathway, and promoting inflammatory responses in colon might act as a causal role in UC. |
| abstractGer |
Background Ulcerative colitis (UC) is an idiopathic colonic mucosal disease, and its pathogenesis has not been fully understood. Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. Aim The present study aimed to validate the underlying mechanism of UPF1 in UC. Methods UPF1 expression was detected by qRT-PCR, western blotting, and immunohistochemistry in dextran sulfate sodium-induced colitis in mice. To simulate the intestinal inflammation microenvironment, NCM460 human colonic epithelial cells were exposed to a mixture of inflammatory mediators. The potential mechanism involving TNFR1-NF-κB/MAPKs pathway activation was addressed by western blotting, reporter gene assays, and siRNA (siUPF1) or UPF1-expressing plasmid pENTER-transfected cells. Results UPF1 was downregulated in colonic epithelial cells of colitic mice, and in vitro, contrary to the mRNA levels of the associated cytokines enhanced in the UPF1 dysregulation group within stimulatory factors, most relevant cytokines were significantly decreased in UPF1 overexpression group. Mechanistically, the increased expression of tumor necrosis factor receptor 1 (TNFR1) was found in NCM460 cells pre-treated with siUPF1, with the activation of IKK/NF-κB and MAPKs pathways, including JNK/AP-1 and P38, but not the ERK1/2 pathway. Moreover, the repression of TNFR1 required the interaction of UPF1 with the promoter. Conclusion UPF1, which negatively regulated the transcription of TNFR1, is a novel factor regulating intestinal inflammation. The downregulation of UPF1 activated the TNFR1-dependent NF-κB/MAPKs pathway, and promoting inflammatory responses in colon might act as a causal role in UC. |
| abstract_unstemmed |
Background Ulcerative colitis (UC) is an idiopathic colonic mucosal disease, and its pathogenesis has not been fully understood. Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. Aim The present study aimed to validate the underlying mechanism of UPF1 in UC. Methods UPF1 expression was detected by qRT-PCR, western blotting, and immunohistochemistry in dextran sulfate sodium-induced colitis in mice. To simulate the intestinal inflammation microenvironment, NCM460 human colonic epithelial cells were exposed to a mixture of inflammatory mediators. The potential mechanism involving TNFR1-NF-κB/MAPKs pathway activation was addressed by western blotting, reporter gene assays, and siRNA (siUPF1) or UPF1-expressing plasmid pENTER-transfected cells. Results UPF1 was downregulated in colonic epithelial cells of colitic mice, and in vitro, contrary to the mRNA levels of the associated cytokines enhanced in the UPF1 dysregulation group within stimulatory factors, most relevant cytokines were significantly decreased in UPF1 overexpression group. Mechanistically, the increased expression of tumor necrosis factor receptor 1 (TNFR1) was found in NCM460 cells pre-treated with siUPF1, with the activation of IKK/NF-κB and MAPKs pathways, including JNK/AP-1 and P38, but not the ERK1/2 pathway. Moreover, the repression of TNFR1 required the interaction of UPF1 with the promoter. Conclusion UPF1, which negatively regulated the transcription of TNFR1, is a novel factor regulating intestinal inflammation. The downregulation of UPF1 activated the TNFR1-dependent NF-κB/MAPKs pathway, and promoting inflammatory responses in colon might act as a causal role in UC. |
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Dysregulated Up-Frameshift Protein 1 Promotes Ulcerative Colitis Pathogenesis Through the TNFR1-NF-κB/MAPKs Pathway |
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https://dx.doi.org/10.1007/s10620-018-5171-8 |
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Huang, Shujun Yue, Min Chen, Wenguo Lu, Chao Lou, Xinhe Li, Chunxiao Shan, Guodong Chen, Hongtan Xu, Xiaowei Xu, Guoqiang Chen, Lihua |
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Huang, Shujun Yue, Min Chen, Wenguo Lu, Chao Lou, Xinhe Li, Chunxiao Shan, Guodong Chen, Hongtan Xu, Xiaowei Xu, Guoqiang Chen, Lihua |
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320525384 |
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10.1007/s10620-018-5171-8 |
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2024-07-04T00:54:29.939Z |
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Up-frameshift protein 1 (UPF1) is a potential molecule for UC predicted by a computational approach. Aim The present study aimed to validate the underlying mechanism of UPF1 in UC. Methods UPF1 expression was detected by qRT-PCR, western blotting, and immunohistochemistry in dextran sulfate sodium-induced colitis in mice. To simulate the intestinal inflammation microenvironment, NCM460 human colonic epithelial cells were exposed to a mixture of inflammatory mediators. The potential mechanism involving TNFR1-NF-κB/MAPKs pathway activation was addressed by western blotting, reporter gene assays, and siRNA (siUPF1) or UPF1-expressing plasmid pENTER-transfected cells. Results UPF1 was downregulated in colonic epithelial cells of colitic mice, and in vitro, contrary to the mRNA levels of the associated cytokines enhanced in the UPF1 dysregulation group within stimulatory factors, most relevant cytokines were significantly decreased in UPF1 overexpression group. Mechanistically, the increased expression of tumor necrosis factor receptor 1 (TNFR1) was found in NCM460 cells pre-treated with siUPF1, with the activation of IKK/NF-κB and MAPKs pathways, including JNK/AP-1 and P38, but not the ERK1/2 pathway. Moreover, the repression of TNFR1 required the interaction of UPF1 with the promoter. Conclusion UPF1, which negatively regulated the transcription of TNFR1, is a novel factor regulating intestinal inflammation. 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