These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: [Adiponectin inhibits the activation of hepatic stellate cells induced by TGFb1 via up-regulating the expression of eNOS].
    Author: Wang W, Zhao CY, Wang YD, He X, Shen C, Cao W, Zhou JY, Zhen Z.
    Journal: Zhonghua Gan Zang Bing Za Zhi; 2011 Dec; 19(12):917-22. PubMed ID: 22525505.
    Abstract:
    OBJECTIVE: To investigate the molecular mechanism of adiponectin inhibiting activation of hepatic stellate cells in non-alcoholic fatty liver fibrosis. METHODS: The rat models of non-alcoholic fatty liver fibrosis were successfully established by fat-rich diet administration. The expression of adiponectin mRNA and protein were respectively detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. LX-2 cells were cultured in an adipogenic differentiation mixture to induce quiescent adipocytic phenotypes, and then they were treated with TGFβ1, adiponectin and TGFβ1 + adiponectin, respectively. RT-PCR and Western blot were used to determine the expressions of mRNAs and proteins of a-smooth muscle actin (a-SMA), Collagen, adenosine monophosphate-activated protein kinase (AMPK), inducible nitric oxide synthase (iNOS), and endothelial NOS (eNOS). The results were analyzed using one-way ANOVA, Student-Newman-Keuls test, and linear correlation analysis. A P value of less than 0.05 was considered as statistically significant. RESULTS: In vivo, with the progress of non-alcoholic fatty liver fibrosis, the model rats gradually showed hepatic steatosis, inflammation, necrosis and fibrosis. Compared with the control group, the level of serum adiponectin (2.49 ± 0.86 vs 5.81 ± 0.87, P < 0.05) and hepatic expressions of adiponectin mRNA and protein (0.26 ± 0.04 vs 0.72 ± 0.08; 0.64 ± 0.07 vs 0.21 ± 0.07, all P < 0.05) were all decreased in the 24th week group, and were negatively correlated with the level of Collagen which increased gradually. In vitro, TGFβ1 could activate quiescent LX-2 cells by decreasing mRNA and protein expression of eNOS (0.30 ± 0.10 vs 0.44 ± 0.08; 0.30 ± 0.09 vs 0.46 ± 0.07, all P < 0.05) and increasing the expression of iNOS (0.53 ± 0.07 vs 0.37 ± 0.04; 0.55 ± 0.07 vs 0.39 ± 0.05, all P < 0.05). Recombinant adiponectin not only maintained the quiescent phenotype of LX-2 cells but also inhibited LX-2 cells activation due to TGFβ1 by increasing the expression of eNOS (0.43 ± 0.08 vs 0.30 ± 0.10; 0.42 ± 0.07 vs 0.30 ± 0.09, all P < 0.05) and phosphorylation of AMPK (0.43 ± 0.07 vs 0.24 ± 0.04, P < 0.05) and decreasing the expression of iNOS (0.44 ± 0.05 vs 0.53 ± 0.07; 0.46 ± 0.07 vs 0.55 ± 0.07, all P < 0.05). CONCLUSIONS: Data suggested that adiponectin could play a protective role on the pathogenesis of non-alcoholic fatty liver fibrosis by inhibiting the activation of hepatic stellate cells via up-regulating the expression of eNOS, which might associate with increased phosphorylation of AMPK.
    [Abstract] [Full Text] [Related] [New Search]