IGFBPrP1 induces liver fibrosis by inducing hepatic stellate cell activation and hepatocyte apoptosis via Smad2/3 signaling

Figure 4 Smad2/3 expression in insulin-like growth factor binding protein-related protein 1-induced rat hepatic fibrosis. Rats were injected with cDNA (cAd) or adenovirus vector carrying insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) (AdIGFBPrP1) and sacrificed 28 d after injection. A-J: Protein expression of IGFBPrP1 in hepatocytes and hepatic stellate cells (HSCs) (arrows) in the livers of cAd-treated (A) and AdIGFBPrP1-treated (B) rats was evaluated by immunofluorescence; Histopathology (C, D) and collagen content (E, F) in the livers of cAd-treated and AdIGFBPrP1-treated rats were demonstrated by HE and Sirius Red staining; expression of total Smad2/3 (G, H) and phosphorylated Smad2/3 (I, J) in hepatocytes and HSCs (arrows) in the livers of cAd-treated and AdIGFBPrP1-treated rats was examined by immunohistochemistry (magnification × 400); K: Protein expression of total and phosphorylated Smad2/3 in the livers was examined by Western blot analysis; L: P-Smad2/3 content normalized with Smad3 content in the livers of the control, cAd or IGFBPrP1 group. Data are expressed as mean ± SD (n = 10 per group). ^aP < 0.05 vs the levels in the control group.