Adiponectin modulates focal adhesion disassembly in activated hepatic stellate cells: implication for reversing hepatic fibrosis

Previous evidence indicates that adiponectin possesses antifibrogenic activity in inhibiting liver fibrosis. Therapeutic strategies, however, are limited by adiponectin quaternary structure and effective concentrations in circulation. Here we postulate a novel molecular mechanism, whereby adiponectin targets focal adhesion kinase (FAK) activity and disrupts key features of the fibrogenic response. Adiponectin-null (Ad−/−) mice and wild-type littermates were exposed to either saline or carbon tetrachloride (CCl4) for 6 wk. CCl4-gavaged mice were also injected with attenuated adenoviral adiponectin (Ad-Adn) or Ad-LacZ for 2 wk. Hepatic stellate cells (HSCs) were treated with or without adiponectin to elucidate signal transduction mechanisms. In vivo delivery of Ad-Adn markedly attenuates CCl4-induced expression of key integrin proteins and markers of HSC activation: αv, β3, β1, α2(I) collagen, and α-smooth muscle actin. Confocal experiments of liver tissues demonstrated that adiponectin delivery also suppre...