Role of transforming growth factor-beta signaling pathway in pathogenesis of benign biliary stricture.

ABSTRACT

AIM: To characterize the expression of members of the transforming growth factor-beta (TGF-beta)/Smad/connective tissue growth factor (CTGF) signaling pathway in the tissue of benign biliary stricture, and to investigate the effect of TGF-beta signaling pathway in the pathogenesis of benign biliary stricture. METHODS: Paraffin embedded materials from 23 cases of benign biliary stricture were analyzed for members of the TGF-beta/Smad/CTGF signaling pathway. TGF-beta (1), TbetaR I , TbetaR II , Smad4, Smad7 and CTGF protein were detected by immunohistochemical strepto-advidinbiotin complex method, and CTGF mRNA was evaluated by hybridization in situ, while 6 cases of normal bile duct served as controls. The percentages of positive cells were counted. The correlation between TGF-beta (1), Smad4 and CTGF was analyzed. RESULTS: The positive expression ratios of TGF-beta (1), TbetaR I , TbetaR II , Smad4, CTGF and CTGF mRNA in 23 cases with benign biliary stricture were 91.3%, 82.6%, 87.0%, 78.3%, 82.6% and 65.2%, respectively, significantly higher than that in 6 cases of normal bile duct respectively (vs 33.3%, 16.7%, 50.0%, 33.3%, 50.0%, 16.7%, respectively, P < 0.05). The positive expression ratio of Smad7 in cases with benign biliary stricture was 70.0%, higher than that in normal bile duct, but this difference is not statistically significant 70.0% vs 50%, P > 0.05). There was a positive correlation between positive expression of TGF-beta (1), Smad4 and CTGF in cases with benign biliary stricture. CONCLUSION: The high expression of TGF-beta/Smad/CTGF signaling pathway plays an important role in the pathogenesis of benign biliary stricture.