Metformin attenuates motility, contraction, and fibrogenic response of hepatic stellate cells in vivo and in vitro by activating AMP-activated protein kinase

Figure 7 The inhibitory effects of metformin on activated hepatic stellate cells were associated with activation of AMPK and subsequent down-regulation of the Akt/mTOR and ERK signaling pathways. A and B: HSCs were pretreated with AICAR (500 μmol/L), LY294002 (20 μmol/L), PD98059 (10 μmol/L), or rapamycin (100 nmol/L) for 2 h and then incubated with PDGF-BB (10 ng/mL) for 24 h. Expression levels of fibronectin (FN), collagen type I (COL1A2), and α-SMA were measured by Western blot analysis and the results were quantified; C and D: HSCs were pretreated with AICAR (500 μmol/L), LY294002 (20 μmol/L), PD98059 (10 μmol/L), or rapamycin (100 nmol/L) for 2 h and then incubated with or without CoCl₂ (150 μmol/L) for 12 h. Expression levels of HIF-1α and VEGF were measured by Western blot analysis; E and F: The results were quantified. (^aP < 0.05 and ^bP < 0.01 vs the control group, ^cP < 0.05 and ^dP < 0.01 vs the PDGF-BB or CoCl₂ only groups). HSCs: Hepatic stellate cells.