Adiponectin attenuates liver fibrosis by inducing nitric oxide production of hepatic stellate cells
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| 024 | 7 | 0 | |a 10.1007/s00109-015-1313-z |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00109-015-1313-z | ||
| 245 | 0 | 0 | |a Adiponectin attenuates liver fibrosis by inducing nitric oxide production of hepatic stellate cells |h [Elektronische Daten] |c [Zhixia Dong, Lin Su, Saeed Esmaili, Tristan Iseli, Mehdi Ramezani-Moghadam, Liangshuo Hu, Aimin Xu, Jacob George, Jianhua Wang] |
| 520 | 3 | |a Adiponectin protects against liver fibrosis, but the mechanisms have not been fully elucidated. Here, we showed that adiponectin upregulated inducible nitric oxide synthase (iNOS) messenger RNA (mRNA) and protein expression in hepatic non-parenchymal cells, particularly in hepatic stellate cells (HSCs), and increased nitric oxide (NO2−/NO3−) concentration in HSC-conditioned medium. Adiponectin attenuated HSC proliferation and migration but promoted apoptosis in a NO-dependent manner. More advanced liver fibrosis with decreased iNOS/NO levels was observed in adiponectin knockout mice comparing to wide-type mice when administered with CCI4 while NO donor supplementation rescued the phenotype. Further experiments demonstrated that adiponectin-induced iNOS/NO system activation is mediated through adipoR2-AMPK-JNK/Erk1/2-NF-κB signaling. These data suggest that adiponectin inhibits HSC function, further limiting the development of liver fibrosis at least in part through adiponectin-induced NO release. Therefore, adiponectin-mediated NO signaling may be a novel target for the treatment of liver fibrosis. Key messages: • Adiponectin activates HSC iNOS/NO and SEC eNOS/NO systems. • Adiponectin inhibits HSC proliferation and migration but promotes its apoptosis. • Adiponectin inhibits CCL4-induced liver fibrosis by modulation of liver iNOS/NO. • Adiponectin stimulates HSC iNOS/NO via adipoR2-AMPK-JNK/ErK1/2-NF-κB pathway. | |
| 540 | |a Springer-Verlag Berlin Heidelberg, 2015 | ||
| 690 | 7 | |a Adiponectin |2 nationallicence | |
| 690 | 7 | |a Hepatic stellate cell |2 nationallicence | |
| 690 | 7 | |a Inducible nitric oxide synthase |2 nationallicence | |
| 690 | 7 | |a The AMP-activated protein kinase |2 nationallicence | |
| 690 | 7 | |a AD : Adiponectin |2 nationallicence | |
| 690 | 7 | |a AD KO : Adiponectin knockout |2 nationallicence | |
| 690 | 7 | |a AMPK : Adenosine monophosphate-activated protein kinase |2 nationallicence | |
| 690 | 7 | |a αSMA : Alpha smooth muscle actin |2 nationallicence | |
| 690 | 7 | |a CCL4 : Carbon tetrachloride |2 nationallicence | |
| 690 | 7 | |a Erk1/2 : Extracellular signal-regulated kinase1/2 |2 nationallicence | |
| 690 | 7 | |a HSCs : Hepatic stellate cells |2 nationallicence | |
| 690 | 7 | |a iNOS : Inducible nitric oxide synthase |2 nationallicence | |
| 690 | 7 | |a JNK : c-Jun terminal kinase |2 nationallicence | |
| 690 | 7 | |a l -NAME : NG-nitro-l-arginine methyl ester, hydrochloride |2 nationallicence | |
| 690 | 7 | |a MAPK : Ras-mitogen-activated protein kinase |2 nationallicence | |
| 690 | 7 | |a NO : Nitric oxide |2 nationallicence | |
| 690 | 7 | |a nNOS : Neuronal nitric oxide synthase |2 nationallicence | |
| 690 | 7 | |a NF-κB : Nuclear factor kappa B |2 nationallicence | |
| 690 | 7 | |a PDGF : Platelet-derived growth factor |2 nationallicence | |
| 690 | 7 | |a PDTC : Ammonium pyrrolidinedithiocarbamate |2 nationallicence | |
| 690 | 7 | |a SECs : Sinusoidal endothelial cells |2 nationallicence | |
| 690 | 7 | |a siRNA : Small interfering RNA |2 nationallicence | |
| 690 | 7 | |a SMT : S-methylisothiourea hemisulfate salt |2 nationallicence | |
| 690 | 7 | |a TGFβ1 : Transforming growth factor beta 1 |2 nationallicence | |
| 690 | 7 | |a WT : Wide type |2 nationallicence | |
| 700 | 1 | |a Dong |D Zhixia |u Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China |4 aut | |
| 700 | 1 | |a Su |D Lin |u Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, 2145, Westmead, NSW, Australia |4 aut | |
| 700 | 1 | |a Esmaili |D Saeed |u Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, 2145, Westmead, NSW, Australia |4 aut | |
| 700 | 1 | |a Iseli |D Tristan |u Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, 2145, Westmead, NSW, Australia |4 aut | |
| 700 | 1 | |a Ramezani-Moghadam |D Mehdi |u Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, 2145, Westmead, NSW, Australia |4 aut | |
| 700 | 1 | |a Hu |D Liangshuo |u Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, 2145, Westmead, NSW, Australia |4 aut | |
| 700 | 1 | |a Xu |D Aimin |u State Key Laboratory of Pharmaceutical Biotechnology, and Department of Medicine, the University of Hong Kong, Hong Kong, Hong Kong |4 aut | |
| 700 | 1 | |a George |D Jacob |u Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, 2145, Westmead, NSW, Australia |4 aut | |
| 700 | 1 | |a Wang |D Jianhua |u Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, 2145, Westmead, NSW, Australia |4 aut | |
| 773 | 0 | |t Journal of Molecular Medicine |d Springer Berlin Heidelberg |g 93/12(2015-12-01), 1327-1339 |x 0946-2716 |q 93:12<1327 |1 2015 |2 93 |o 109 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00109-015-1313-z |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00109-015-1313-z |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Dong |D Zhixia |u Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Su |D Lin |u Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, 2145, Westmead, NSW, Australia |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Esmaili |D Saeed |u Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, 2145, Westmead, NSW, Australia |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Iseli |D Tristan |u Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, 2145, Westmead, NSW, Australia |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Ramezani-Moghadam |D Mehdi |u Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, 2145, Westmead, NSW, Australia |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Hu |D Liangshuo |u Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, 2145, Westmead, NSW, Australia |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Xu |D Aimin |u State Key Laboratory of Pharmaceutical Biotechnology, and Department of Medicine, the University of Hong Kong, Hong Kong, Hong Kong |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a George |D Jacob |u Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, 2145, Westmead, NSW, Australia |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Wang |D Jianhua |u Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, 2145, Westmead, NSW, Australia |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Journal of Molecular Medicine |d Springer Berlin Heidelberg |g 93/12(2015-12-01), 1327-1339 |x 0946-2716 |q 93:12<1327 |1 2015 |2 93 |o 109 | ||