Effect of insulin-like growth factor binding protein-related protein 1 in the formation and development of hepatic fibrosis

Abstract

Objective To investigate the effect of insulin-like growth factor binding protein-related protein 1 ( IGFBPrP1 ) in the formation and development of hepatic fibrosis. Methods Hepatic fibrosis model of mice was made by intraperitoneal injecting with thioacetamide, then the mice were sacrificed four, five and six weeks later (10 mice were sacrificed at each time point, model groups). Mice in the control groups were treated by normal saline (6 mice were sacrificed at each time point). Collagen accumulation in liver tissues was detected by Masson stain. Distribution and dynamic expressions of IGFBPrP1, alpha-smooth muscle actin ( α-SMA ),Collagen Ⅰ , fibronectin ( FN), TGF-β1 and Smad3 in different groups were detected by immunohistochemistry.The expressions of IGFBPrP1, α-SMA and Smad3 were detected by Western blot. All data were analyzed using the analysis of variance (ANOVA), Pearson rank correlation coefficient. Results The expressions of IGFBPrP1 in the liver tissues were increased from 0.21 ±0.03 to 5.03 ±0.09, α-SMA from 0. 11 ±0.04 to 10.09 ±0. 18,Collagen Ⅰ from 0.22 ±0.01 to 11.01 ±0. 16, FN from 0.31 ±0.09 to 19.81 ±1.62, TGF-β1 from 0.49 ±0.02 to 5.97 ± 0. 19, and Smad3 from 0.22 ± 0.03 to 2.03 ± 0.07. Compared with the control groups, the expressions of IGFBPrP1, α-SMA, Collagen Ⅰ , FN, TGF-β1 and Smad3 in the model groups were significantly increased as time passed by ( F = 783. 141,998. 200,886. 715,935. 242, 931. 241,697. 118, P < 0. 05 ). During the formation of hepatic fibrosis, the expression of IGFBPrP1 was positively correlated with the expressions of α-SMA,Collagen Ⅰ , FN, TGF-β1 and Smad3 ( r = 0. 906, 0. 927, 0. 988, 0. 947, 0. 977, P < 0.05 ). The results of Western blot showed that the protein expression of IGFBPrP1 was increased from 0. 23 ± 0.01 to 0.92 ± 0.07,α-SMA from 0.36 ± 0. 02 to 1.39 ± 0.03, FN from 0.03 ± 0.00 to 0.12 ± 0.02, and Smad3 from 0.09 ± 0. 01 to 0.56 ±0.04. The protein expressions of IGFBPrP1, α-SMA, FN and Smad3 were significantly increased in the model groups when compared with the control groups (F =57. 316, 201. 214, 103. 871, 72. 966, P <0.05).During the formation of hepatic fibrosis. IGFBPrP1 was positively correlated with the expressions of α-SMA, FN and Smad3 (r = 0. 982, 0. 924, 0. 965, P < 0.05 ). Conclusions The expression of IGFBPrP1 increases as the aggravation of the fibrosis. IGFBPrP1 promotes the formation and development of hepatic fibrosis by activating hepatic stellate cells, accelerating the synthesis and secretion of Collagen Ⅰ and FN which are the principal components of extracellular matrix, and affecting the TGF-β1/Smad3 pathway. Key words: Liver cirrhosis; Insulin-like growth factor binding protein-related protein 1; Transforming growth factor-β1; Smad3