N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. The disease involves excessive accumulation of fibroblasts and myofibroblasts, and myofibroblasts differentiated by pro-fibrotic factors promote the deposition of extracellular matrix proteins such as collagen and fibronectin...
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Autor*in:	Nakamura, Hiroyuki [verfasserIn] Zhou, Yuan [verfasserIn] Sakamoto, Yuka [verfasserIn] Yamazaki, Ayako [verfasserIn] Kurumiya, Eon [verfasserIn] Yamazaki, Risa [verfasserIn] Hayashi, Kyota [verfasserIn] Kasuya, Yoshitoshi [verfasserIn] Watanabe, Kazuaki [verfasserIn] Kasahara, Junya [verfasserIn] Takabatake, Mamoru [verfasserIn] Tatsumi, Koichiro [verfasserIn] Yoshino, Ichiro [verfasserIn] Honda, Takuya [verfasserIn] Murayama, Toshihiko [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Iminosugar N-butyldeoxynojirimycin Pulmonary fibrosis Smad Transforming growth factor-β

Übergeordnetes Werk:	Enthalten in: Biomedicine & pharmacotherapy - Amsterdam [u.a.] : Elsevier Science, 1989, 160
Übergeordnetes Werk:	volume:160

DOI / URN:	10.1016/j.biopha.2023.114405

Katalog-ID:	ELV065421817

Internformat


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024	7		\|a 10.1016/j.biopha.2023.114405 \|2 doi
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100	1		\|a Nakamura, Hiroyuki \|e verfasserin \|0 (orcid)0000-0001-6328-9727 \|4 aut
245	1	0	\|a N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3
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520			\|a Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. The disease involves excessive accumulation of fibroblasts and myofibroblasts, and myofibroblasts differentiated by pro-fibrotic factors promote the deposition of extracellular matrix proteins such as collagen and fibronectin. Transforming growth factor-β1 is a pro-fibrotic factor that promotes fibroblast-to-myofibroblast differentiation (FMD). Therefore, inhibition of FMD may be an effective strategy for IPF treatment. In this study, we screened the anti-FMD effects of various iminosugars and showed that some compounds, including N-butyldeoxynojirimycin (NB-DNJ, miglustat, an inhibitor of glucosylceramide synthase (GCS)), a clinically approved drug for treating Niemann–Pick disease type C and Gaucher disease type 1, inhibited TGF-β1-induced FMD by inhibiting the nuclear translocation of Smad2/3. N-butyldeoxygalactonojirimycin having GCS inhibitory effect did not attenuate the TGF-β1-induced FMD, suggesting that NB-DNJ exerts the anti-FMD effects by GCS inhibitory effect independent manner. N-butyldeoxynojirimycin did not inhibit TGF-β1-induced Smad2/3 phosphorylation. In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, intratracheal or oral administration of NB-DNJ at an early fibrotic stage markedly ameliorated lung injury and deterioration of respiratory functions, such as specific airway resistance, tidal volume, and peak expiratory flow. Furthermore, the anti-fibrotic effects of NB-DNJ in the BLM-induced lung injury model were similar to those of pirfenidone and nintedanib, which are clinically approved drugs for the treatment of IPF. These results suggest that NB-DNJ may be effective for IPF treatment.
650		4	\|a Iminosugar
650		4	\|a N-butyldeoxynojirimycin
650		4	\|a Pulmonary fibrosis
650		4	\|a Smad
650		4	\|a Transforming growth factor-β
700	1		\|a Zhou, Yuan \|e verfasserin \|4 aut
700	1		\|a Sakamoto, Yuka \|e verfasserin \|4 aut
700	1		\|a Yamazaki, Ayako \|e verfasserin \|0 (orcid)0000-0003-0168-4574 \|4 aut
700	1		\|a Kurumiya, Eon \|e verfasserin \|4 aut
700	1		\|a Yamazaki, Risa \|e verfasserin \|0 (orcid)0000-0001-9717-6763 \|4 aut
700	1		\|a Hayashi, Kyota \|e verfasserin \|4 aut
700	1		\|a Kasuya, Yoshitoshi \|e verfasserin \|4 aut
700	1		\|a Watanabe, Kazuaki \|e verfasserin \|4 aut
700	1		\|a Kasahara, Junya \|e verfasserin \|4 aut
700	1		\|a Takabatake, Mamoru \|e verfasserin \|4 aut
700	1		\|a Tatsumi, Koichiro \|e verfasserin \|4 aut
700	1		\|a Yoshino, Ichiro \|e verfasserin \|4 aut
700	1		\|a Honda, Takuya \|e verfasserin \|0 (orcid)0000-0002-7141-0088 \|4 aut
700	1		\|a Murayama, Toshihiko \|e verfasserin \|4 aut
773	0	8	\|i Enthalten in \|t Biomedicine & pharmacotherapy \|d Amsterdam [u.a.] : Elsevier Science, 1989 \|g 160 \|h Online-Ressource \|w (DE-627)306717565 \|w (DE-600)1501510-5 \|w (DE-576)261593021 \|x 1950-6007 \|7 nnns
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912			\|a GBV_ILN_105
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912			\|a GBV_ILN_151
912			\|a GBV_ILN_161
912			\|a GBV_ILN_165
912			\|a GBV_ILN_170
912			\|a GBV_ILN_206
912			\|a GBV_ILN_213
912			\|a GBV_ILN_224
912			\|a GBV_ILN_230
912			\|a GBV_ILN_285
912			\|a GBV_ILN_293
912			\|a GBV_ILN_602
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912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
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912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
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912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4367
912			\|a GBV_ILN_4700
936	b	k	\|a 44.40 \|j Pharmazie \|j Pharmazeutika \|q VZ
951			\|a AR
952			\|d 160

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publishDate	2023
allfields	10.1016/j.biopha.2023.114405 doi (DE-627)ELV065421817 (ELSEVIER)S0753-3322(23)00193-2 DE-627 ger DE-627 rda eng 610 VZ 44.40 bkl Nakamura, Hiroyuki verfasserin (orcid)0000-0001-6328-9727 aut N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. The disease involves excessive accumulation of fibroblasts and myofibroblasts, and myofibroblasts differentiated by pro-fibrotic factors promote the deposition of extracellular matrix proteins such as collagen and fibronectin. Transforming growth factor-β1 is a pro-fibrotic factor that promotes fibroblast-to-myofibroblast differentiation (FMD). Therefore, inhibition of FMD may be an effective strategy for IPF treatment. In this study, we screened the anti-FMD effects of various iminosugars and showed that some compounds, including N-butyldeoxynojirimycin (NB-DNJ, miglustat, an inhibitor of glucosylceramide synthase (GCS)), a clinically approved drug for treating Niemann–Pick disease type C and Gaucher disease type 1, inhibited TGF-β1-induced FMD by inhibiting the nuclear translocation of Smad2/3. N-butyldeoxygalactonojirimycin having GCS inhibitory effect did not attenuate the TGF-β1-induced FMD, suggesting that NB-DNJ exerts the anti-FMD effects by GCS inhibitory effect independent manner. N-butyldeoxynojirimycin did not inhibit TGF-β1-induced Smad2/3 phosphorylation. In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, intratracheal or oral administration of NB-DNJ at an early fibrotic stage markedly ameliorated lung injury and deterioration of respiratory functions, such as specific airway resistance, tidal volume, and peak expiratory flow. Furthermore, the anti-fibrotic effects of NB-DNJ in the BLM-induced lung injury model were similar to those of pirfenidone and nintedanib, which are clinically approved drugs for the treatment of IPF. These results suggest that NB-DNJ may be effective for IPF treatment. Iminosugar N-butyldeoxynojirimycin Pulmonary fibrosis Smad Transforming growth factor-β Zhou, Yuan verfasserin aut Sakamoto, Yuka verfasserin aut Yamazaki, Ayako verfasserin (orcid)0000-0003-0168-4574 aut Kurumiya, Eon verfasserin aut Yamazaki, Risa verfasserin (orcid)0000-0001-9717-6763 aut Hayashi, Kyota verfasserin aut Kasuya, Yoshitoshi verfasserin aut Watanabe, Kazuaki verfasserin aut Kasahara, Junya verfasserin aut Takabatake, Mamoru verfasserin aut Tatsumi, Koichiro verfasserin aut Yoshino, Ichiro verfasserin aut Honda, Takuya verfasserin (orcid)0000-0002-7141-0088 aut Murayama, Toshihiko verfasserin aut Enthalten in Biomedicine & pharmacotherapy Amsterdam [u.a.] : Elsevier Science, 1989 160 Online-Ressource (DE-627)306717565 (DE-600)1501510-5 (DE-576)261593021 1950-6007 nnns volume:160 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 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_4338 GBV_ILN_4367 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika VZ AR 160
spelling	10.1016/j.biopha.2023.114405 doi (DE-627)ELV065421817 (ELSEVIER)S0753-3322(23)00193-2 DE-627 ger DE-627 rda eng 610 VZ 44.40 bkl Nakamura, Hiroyuki verfasserin (orcid)0000-0001-6328-9727 aut N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. The disease involves excessive accumulation of fibroblasts and myofibroblasts, and myofibroblasts differentiated by pro-fibrotic factors promote the deposition of extracellular matrix proteins such as collagen and fibronectin. Transforming growth factor-β1 is a pro-fibrotic factor that promotes fibroblast-to-myofibroblast differentiation (FMD). Therefore, inhibition of FMD may be an effective strategy for IPF treatment. In this study, we screened the anti-FMD effects of various iminosugars and showed that some compounds, including N-butyldeoxynojirimycin (NB-DNJ, miglustat, an inhibitor of glucosylceramide synthase (GCS)), a clinically approved drug for treating Niemann–Pick disease type C and Gaucher disease type 1, inhibited TGF-β1-induced FMD by inhibiting the nuclear translocation of Smad2/3. N-butyldeoxygalactonojirimycin having GCS inhibitory effect did not attenuate the TGF-β1-induced FMD, suggesting that NB-DNJ exerts the anti-FMD effects by GCS inhibitory effect independent manner. N-butyldeoxynojirimycin did not inhibit TGF-β1-induced Smad2/3 phosphorylation. In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, intratracheal or oral administration of NB-DNJ at an early fibrotic stage markedly ameliorated lung injury and deterioration of respiratory functions, such as specific airway resistance, tidal volume, and peak expiratory flow. Furthermore, the anti-fibrotic effects of NB-DNJ in the BLM-induced lung injury model were similar to those of pirfenidone and nintedanib, which are clinically approved drugs for the treatment of IPF. These results suggest that NB-DNJ may be effective for IPF treatment. Iminosugar N-butyldeoxynojirimycin Pulmonary fibrosis Smad Transforming growth factor-β Zhou, Yuan verfasserin aut Sakamoto, Yuka verfasserin aut Yamazaki, Ayako verfasserin (orcid)0000-0003-0168-4574 aut Kurumiya, Eon verfasserin aut Yamazaki, Risa verfasserin (orcid)0000-0001-9717-6763 aut Hayashi, Kyota verfasserin aut Kasuya, Yoshitoshi verfasserin aut Watanabe, Kazuaki verfasserin aut Kasahara, Junya verfasserin aut Takabatake, Mamoru verfasserin aut Tatsumi, Koichiro verfasserin aut Yoshino, Ichiro verfasserin aut Honda, Takuya verfasserin (orcid)0000-0002-7141-0088 aut Murayama, Toshihiko verfasserin aut Enthalten in Biomedicine & pharmacotherapy Amsterdam [u.a.] : Elsevier Science, 1989 160 Online-Ressource (DE-627)306717565 (DE-600)1501510-5 (DE-576)261593021 1950-6007 nnns volume:160 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 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_4338 GBV_ILN_4367 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika VZ AR 160
allfields_unstemmed	10.1016/j.biopha.2023.114405 doi (DE-627)ELV065421817 (ELSEVIER)S0753-3322(23)00193-2 DE-627 ger DE-627 rda eng 610 VZ 44.40 bkl Nakamura, Hiroyuki verfasserin (orcid)0000-0001-6328-9727 aut N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. The disease involves excessive accumulation of fibroblasts and myofibroblasts, and myofibroblasts differentiated by pro-fibrotic factors promote the deposition of extracellular matrix proteins such as collagen and fibronectin. Transforming growth factor-β1 is a pro-fibrotic factor that promotes fibroblast-to-myofibroblast differentiation (FMD). Therefore, inhibition of FMD may be an effective strategy for IPF treatment. In this study, we screened the anti-FMD effects of various iminosugars and showed that some compounds, including N-butyldeoxynojirimycin (NB-DNJ, miglustat, an inhibitor of glucosylceramide synthase (GCS)), a clinically approved drug for treating Niemann–Pick disease type C and Gaucher disease type 1, inhibited TGF-β1-induced FMD by inhibiting the nuclear translocation of Smad2/3. N-butyldeoxygalactonojirimycin having GCS inhibitory effect did not attenuate the TGF-β1-induced FMD, suggesting that NB-DNJ exerts the anti-FMD effects by GCS inhibitory effect independent manner. N-butyldeoxynojirimycin did not inhibit TGF-β1-induced Smad2/3 phosphorylation. In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, intratracheal or oral administration of NB-DNJ at an early fibrotic stage markedly ameliorated lung injury and deterioration of respiratory functions, such as specific airway resistance, tidal volume, and peak expiratory flow. Furthermore, the anti-fibrotic effects of NB-DNJ in the BLM-induced lung injury model were similar to those of pirfenidone and nintedanib, which are clinically approved drugs for the treatment of IPF. These results suggest that NB-DNJ may be effective for IPF treatment. Iminosugar N-butyldeoxynojirimycin Pulmonary fibrosis Smad Transforming growth factor-β Zhou, Yuan verfasserin aut Sakamoto, Yuka verfasserin aut Yamazaki, Ayako verfasserin (orcid)0000-0003-0168-4574 aut Kurumiya, Eon verfasserin aut Yamazaki, Risa verfasserin (orcid)0000-0001-9717-6763 aut Hayashi, Kyota verfasserin aut Kasuya, Yoshitoshi verfasserin aut Watanabe, Kazuaki verfasserin aut Kasahara, Junya verfasserin aut Takabatake, Mamoru verfasserin aut Tatsumi, Koichiro verfasserin aut Yoshino, Ichiro verfasserin aut Honda, Takuya verfasserin (orcid)0000-0002-7141-0088 aut Murayama, Toshihiko verfasserin aut Enthalten in Biomedicine & pharmacotherapy Amsterdam [u.a.] : Elsevier Science, 1989 160 Online-Ressource (DE-627)306717565 (DE-600)1501510-5 (DE-576)261593021 1950-6007 nnns volume:160 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 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_4338 GBV_ILN_4367 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika VZ AR 160
allfieldsGer	10.1016/j.biopha.2023.114405 doi (DE-627)ELV065421817 (ELSEVIER)S0753-3322(23)00193-2 DE-627 ger DE-627 rda eng 610 VZ 44.40 bkl Nakamura, Hiroyuki verfasserin (orcid)0000-0001-6328-9727 aut N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. The disease involves excessive accumulation of fibroblasts and myofibroblasts, and myofibroblasts differentiated by pro-fibrotic factors promote the deposition of extracellular matrix proteins such as collagen and fibronectin. Transforming growth factor-β1 is a pro-fibrotic factor that promotes fibroblast-to-myofibroblast differentiation (FMD). Therefore, inhibition of FMD may be an effective strategy for IPF treatment. In this study, we screened the anti-FMD effects of various iminosugars and showed that some compounds, including N-butyldeoxynojirimycin (NB-DNJ, miglustat, an inhibitor of glucosylceramide synthase (GCS)), a clinically approved drug for treating Niemann–Pick disease type C and Gaucher disease type 1, inhibited TGF-β1-induced FMD by inhibiting the nuclear translocation of Smad2/3. N-butyldeoxygalactonojirimycin having GCS inhibitory effect did not attenuate the TGF-β1-induced FMD, suggesting that NB-DNJ exerts the anti-FMD effects by GCS inhibitory effect independent manner. N-butyldeoxynojirimycin did not inhibit TGF-β1-induced Smad2/3 phosphorylation. In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, intratracheal or oral administration of NB-DNJ at an early fibrotic stage markedly ameliorated lung injury and deterioration of respiratory functions, such as specific airway resistance, tidal volume, and peak expiratory flow. Furthermore, the anti-fibrotic effects of NB-DNJ in the BLM-induced lung injury model were similar to those of pirfenidone and nintedanib, which are clinically approved drugs for the treatment of IPF. These results suggest that NB-DNJ may be effective for IPF treatment. Iminosugar N-butyldeoxynojirimycin Pulmonary fibrosis Smad Transforming growth factor-β Zhou, Yuan verfasserin aut Sakamoto, Yuka verfasserin aut Yamazaki, Ayako verfasserin (orcid)0000-0003-0168-4574 aut Kurumiya, Eon verfasserin aut Yamazaki, Risa verfasserin (orcid)0000-0001-9717-6763 aut Hayashi, Kyota verfasserin aut Kasuya, Yoshitoshi verfasserin aut Watanabe, Kazuaki verfasserin aut Kasahara, Junya verfasserin aut Takabatake, Mamoru verfasserin aut Tatsumi, Koichiro verfasserin aut Yoshino, Ichiro verfasserin aut Honda, Takuya verfasserin (orcid)0000-0002-7141-0088 aut Murayama, Toshihiko verfasserin aut Enthalten in Biomedicine & pharmacotherapy Amsterdam [u.a.] : Elsevier Science, 1989 160 Online-Ressource (DE-627)306717565 (DE-600)1501510-5 (DE-576)261593021 1950-6007 nnns volume:160 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 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_4338 GBV_ILN_4367 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika VZ AR 160
allfieldsSound	10.1016/j.biopha.2023.114405 doi (DE-627)ELV065421817 (ELSEVIER)S0753-3322(23)00193-2 DE-627 ger DE-627 rda eng 610 VZ 44.40 bkl Nakamura, Hiroyuki verfasserin (orcid)0000-0001-6328-9727 aut N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. The disease involves excessive accumulation of fibroblasts and myofibroblasts, and myofibroblasts differentiated by pro-fibrotic factors promote the deposition of extracellular matrix proteins such as collagen and fibronectin. Transforming growth factor-β1 is a pro-fibrotic factor that promotes fibroblast-to-myofibroblast differentiation (FMD). Therefore, inhibition of FMD may be an effective strategy for IPF treatment. In this study, we screened the anti-FMD effects of various iminosugars and showed that some compounds, including N-butyldeoxynojirimycin (NB-DNJ, miglustat, an inhibitor of glucosylceramide synthase (GCS)), a clinically approved drug for treating Niemann–Pick disease type C and Gaucher disease type 1, inhibited TGF-β1-induced FMD by inhibiting the nuclear translocation of Smad2/3. N-butyldeoxygalactonojirimycin having GCS inhibitory effect did not attenuate the TGF-β1-induced FMD, suggesting that NB-DNJ exerts the anti-FMD effects by GCS inhibitory effect independent manner. N-butyldeoxynojirimycin did not inhibit TGF-β1-induced Smad2/3 phosphorylation. In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, intratracheal or oral administration of NB-DNJ at an early fibrotic stage markedly ameliorated lung injury and deterioration of respiratory functions, such as specific airway resistance, tidal volume, and peak expiratory flow. Furthermore, the anti-fibrotic effects of NB-DNJ in the BLM-induced lung injury model were similar to those of pirfenidone and nintedanib, which are clinically approved drugs for the treatment of IPF. These results suggest that NB-DNJ may be effective for IPF treatment. Iminosugar N-butyldeoxynojirimycin Pulmonary fibrosis Smad Transforming growth factor-β Zhou, Yuan verfasserin aut Sakamoto, Yuka verfasserin aut Yamazaki, Ayako verfasserin (orcid)0000-0003-0168-4574 aut Kurumiya, Eon verfasserin aut Yamazaki, Risa verfasserin (orcid)0000-0001-9717-6763 aut Hayashi, Kyota verfasserin aut Kasuya, Yoshitoshi verfasserin aut Watanabe, Kazuaki verfasserin aut Kasahara, Junya verfasserin aut Takabatake, Mamoru verfasserin aut Tatsumi, Koichiro verfasserin aut Yoshino, Ichiro verfasserin aut Honda, Takuya verfasserin (orcid)0000-0002-7141-0088 aut Murayama, Toshihiko verfasserin aut Enthalten in Biomedicine & pharmacotherapy Amsterdam [u.a.] : Elsevier Science, 1989 160 Online-Ressource (DE-627)306717565 (DE-600)1501510-5 (DE-576)261593021 1950-6007 nnns volume:160 GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_165 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2008 GBV_ILN_2014 GBV_ILN_2034 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2064 GBV_ILN_2106 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 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_4338 GBV_ILN_4367 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika VZ AR 160
language	English
source	Enthalten in Biomedicine & pharmacotherapy 160 volume:160
sourceStr	Enthalten in Biomedicine & pharmacotherapy 160 volume:160
format_phy_str_mv	Article
bklname	Pharmazie Pharmazeutika
institution	findex.gbv.de
topic_facet	Iminosugar N-butyldeoxynojirimycin Pulmonary fibrosis Smad Transforming growth factor-β
dewey-raw	610
isfreeaccess_bool	false
container_title	Biomedicine & pharmacotherapy
authorswithroles_txt_mv	Nakamura, Hiroyuki @@aut@@ Zhou, Yuan @@aut@@ Sakamoto, Yuka @@aut@@ Yamazaki, Ayako @@aut@@ Kurumiya, Eon @@aut@@ Yamazaki, Risa @@aut@@ Hayashi, Kyota @@aut@@ Kasuya, Yoshitoshi @@aut@@ Watanabe, Kazuaki @@aut@@ Kasahara, Junya @@aut@@ Takabatake, Mamoru @@aut@@ Tatsumi, Koichiro @@aut@@ Yoshino, Ichiro @@aut@@ Honda, Takuya @@aut@@ Murayama, Toshihiko @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
hierarchy_top_id	306717565
dewey-sort	3610
id	ELV065421817
language_de	englisch
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author	Nakamura, Hiroyuki
spellingShingle	Nakamura, Hiroyuki ddc 610 bkl 44.40 misc Iminosugar misc N-butyldeoxynojirimycin misc Pulmonary fibrosis misc Smad misc Transforming growth factor-β N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3
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topic_title	610 VZ 44.40 bkl N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3 Iminosugar N-butyldeoxynojirimycin Pulmonary fibrosis Smad Transforming growth factor-β
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title	N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3
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title_full	N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3
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author_browse	Nakamura, Hiroyuki Zhou, Yuan Sakamoto, Yuka Yamazaki, Ayako Kurumiya, Eon Yamazaki, Risa Hayashi, Kyota Kasuya, Yoshitoshi Watanabe, Kazuaki Kasahara, Junya Takabatake, Mamoru Tatsumi, Koichiro Yoshino, Ichiro Honda, Takuya Murayama, Toshihiko
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author-letter	Nakamura, Hiroyuki
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title_sort	n-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of smad2/3
title_auth	N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3
abstract	Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. The disease involves excessive accumulation of fibroblasts and myofibroblasts, and myofibroblasts differentiated by pro-fibrotic factors promote the deposition of extracellular matrix proteins such as collagen and fibronectin. Transforming growth factor-β1 is a pro-fibrotic factor that promotes fibroblast-to-myofibroblast differentiation (FMD). Therefore, inhibition of FMD may be an effective strategy for IPF treatment. In this study, we screened the anti-FMD effects of various iminosugars and showed that some compounds, including N-butyldeoxynojirimycin (NB-DNJ, miglustat, an inhibitor of glucosylceramide synthase (GCS)), a clinically approved drug for treating Niemann–Pick disease type C and Gaucher disease type 1, inhibited TGF-β1-induced FMD by inhibiting the nuclear translocation of Smad2/3. N-butyldeoxygalactonojirimycin having GCS inhibitory effect did not attenuate the TGF-β1-induced FMD, suggesting that NB-DNJ exerts the anti-FMD effects by GCS inhibitory effect independent manner. N-butyldeoxynojirimycin did not inhibit TGF-β1-induced Smad2/3 phosphorylation. In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, intratracheal or oral administration of NB-DNJ at an early fibrotic stage markedly ameliorated lung injury and deterioration of respiratory functions, such as specific airway resistance, tidal volume, and peak expiratory flow. Furthermore, the anti-fibrotic effects of NB-DNJ in the BLM-induced lung injury model were similar to those of pirfenidone and nintedanib, which are clinically approved drugs for the treatment of IPF. These results suggest that NB-DNJ may be effective for IPF treatment.
abstractGer	Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. The disease involves excessive accumulation of fibroblasts and myofibroblasts, and myofibroblasts differentiated by pro-fibrotic factors promote the deposition of extracellular matrix proteins such as collagen and fibronectin. Transforming growth factor-β1 is a pro-fibrotic factor that promotes fibroblast-to-myofibroblast differentiation (FMD). Therefore, inhibition of FMD may be an effective strategy for IPF treatment. In this study, we screened the anti-FMD effects of various iminosugars and showed that some compounds, including N-butyldeoxynojirimycin (NB-DNJ, miglustat, an inhibitor of glucosylceramide synthase (GCS)), a clinically approved drug for treating Niemann–Pick disease type C and Gaucher disease type 1, inhibited TGF-β1-induced FMD by inhibiting the nuclear translocation of Smad2/3. N-butyldeoxygalactonojirimycin having GCS inhibitory effect did not attenuate the TGF-β1-induced FMD, suggesting that NB-DNJ exerts the anti-FMD effects by GCS inhibitory effect independent manner. N-butyldeoxynojirimycin did not inhibit TGF-β1-induced Smad2/3 phosphorylation. In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, intratracheal or oral administration of NB-DNJ at an early fibrotic stage markedly ameliorated lung injury and deterioration of respiratory functions, such as specific airway resistance, tidal volume, and peak expiratory flow. Furthermore, the anti-fibrotic effects of NB-DNJ in the BLM-induced lung injury model were similar to those of pirfenidone and nintedanib, which are clinically approved drugs for the treatment of IPF. These results suggest that NB-DNJ may be effective for IPF treatment.
abstract_unstemmed	Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease. The disease involves excessive accumulation of fibroblasts and myofibroblasts, and myofibroblasts differentiated by pro-fibrotic factors promote the deposition of extracellular matrix proteins such as collagen and fibronectin. Transforming growth factor-β1 is a pro-fibrotic factor that promotes fibroblast-to-myofibroblast differentiation (FMD). Therefore, inhibition of FMD may be an effective strategy for IPF treatment. In this study, we screened the anti-FMD effects of various iminosugars and showed that some compounds, including N-butyldeoxynojirimycin (NB-DNJ, miglustat, an inhibitor of glucosylceramide synthase (GCS)), a clinically approved drug for treating Niemann–Pick disease type C and Gaucher disease type 1, inhibited TGF-β1-induced FMD by inhibiting the nuclear translocation of Smad2/3. N-butyldeoxygalactonojirimycin having GCS inhibitory effect did not attenuate the TGF-β1-induced FMD, suggesting that NB-DNJ exerts the anti-FMD effects by GCS inhibitory effect independent manner. N-butyldeoxynojirimycin did not inhibit TGF-β1-induced Smad2/3 phosphorylation. In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, intratracheal or oral administration of NB-DNJ at an early fibrotic stage markedly ameliorated lung injury and deterioration of respiratory functions, such as specific airway resistance, tidal volume, and peak expiratory flow. Furthermore, the anti-fibrotic effects of NB-DNJ in the BLM-induced lung injury model were similar to those of pirfenidone and nintedanib, which are clinically approved drugs for the treatment of IPF. These results suggest that NB-DNJ may be effective for IPF treatment.
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title_short	N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3
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author2	Zhou, Yuan Sakamoto, Yuka Yamazaki, Ayako Kurumiya, Eon Yamazaki, Risa Hayashi, Kyota Kasuya, Yoshitoshi Watanabe, Kazuaki Kasahara, Junya Takabatake, Mamoru Tatsumi, Koichiro Yoshino, Ichiro Honda, Takuya Murayama, Toshihiko
author2Str	Zhou, Yuan Sakamoto, Yuka Yamazaki, Ayako Kurumiya, Eon Yamazaki, Risa Hayashi, Kyota Kasuya, Yoshitoshi Watanabe, Kazuaki Kasahara, Junya Takabatake, Mamoru Tatsumi, Koichiro Yoshino, Ichiro Honda, Takuya Murayama, Toshihiko
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doi_str	10.1016/j.biopha.2023.114405
up_date	2024-07-06T22:58:39.437Z
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The disease involves excessive accumulation of fibroblasts and myofibroblasts, and myofibroblasts differentiated by pro-fibrotic factors promote the deposition of extracellular matrix proteins such as collagen and fibronectin. Transforming growth factor-β1 is a pro-fibrotic factor that promotes fibroblast-to-myofibroblast differentiation (FMD). Therefore, inhibition of FMD may be an effective strategy for IPF treatment. In this study, we screened the anti-FMD effects of various iminosugars and showed that some compounds, including N-butyldeoxynojirimycin (NB-DNJ, miglustat, an inhibitor of glucosylceramide synthase (GCS)), a clinically approved drug for treating Niemann–Pick disease type C and Gaucher disease type 1, inhibited TGF-β1-induced FMD by inhibiting the nuclear translocation of Smad2/3. N-butyldeoxygalactonojirimycin having GCS inhibitory effect did not attenuate the TGF-β1-induced FMD, suggesting that NB-DNJ exerts the anti-FMD effects by GCS inhibitory effect independent manner. N-butyldeoxynojirimycin did not inhibit TGF-β1-induced Smad2/3 phosphorylation. In a mouse model of bleomycin (BLM)-induced pulmonary fibrosis, intratracheal or oral administration of NB-DNJ at an early fibrotic stage markedly ameliorated lung injury and deterioration of respiratory functions, such as specific airway resistance, tidal volume, and peak expiratory flow. Furthermore, the anti-fibrotic effects of NB-DNJ in the BLM-induced lung injury model were similar to those of pirfenidone and nintedanib, which are clinically approved drugs for the treatment of IPF. 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N-butyldeoxynojirimycin (miglustat) ameliorates pulmonary fibrosis through inhibition of nuclear translocation of Smad2/3

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