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World J Gastroenterol. Aug 21, 2008; 14(31): 4949-4954
Published online Aug 21, 2008. doi: 10.3748/wjg.14.4949
Role of transforming growth factor-beta signaling pathway in pathogenesis of benign biliary stricture
Zhi-Min Geng, Jian-Bao Zheng, Xiao-Xue Zhang, Jie Tao, Lin Wang
Zhi-Min Geng, Xiao-Xue Zhang, Jie Tao, Lin Wang, Department of Hepatobiliary Surgery, First Affiliated Hospital, Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Jian-Bao Zheng, Department of General Surgery, First Affiliated Hospital, Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China
Author contributions: Geng ZM and Zheng JB contributed equally to this work; Geng ZM, Zheng JB and Wang L designed research; Geng ZM, Zheng JB, Zhang XX, Tao J performed research; Zheng JB, Zhang XX contributed new analytic tools; Geng ZM, Tao J and Zheng JB analyzed data; and Geng ZM and Zheng JB wrote the paper.
Supported by The grant from Shaanxi Science and Technology Project, No. 2002K10-G8
Correspondence to: Dr. Jian-Bao Zheng, Department of General Surgery, First Affiliated Hospital, Medical College, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, China. bob.zheng@stu.xjtu.edu.cn
Telephone: +86-29-85323870 Fax: +86-29-85323870
Received: May 6, 2008
Revised: July 28, 2008
Accepted: August 4, 2008
Published online: August 21, 2008
Abstract

AIM: To characterize the expression of members of the transforming growth factor-beta (TGF-β)/Smad/connective tissue growth factor (CTGF) signaling pathway in the tissue of benign biliary stricture, and to investigate the effect of TGF-β 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-β/Smad/CTGF signaling pathway. TGF-β1, TβRI, TβRII, 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-β1, Smad4 and CTGF was analyzed.

RESULTS: The positive expression ratios of TGF-β1, TβRI, TβRII, 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-β1, Smad4 and CTGF in cases with benign biliary stricture.

CONCLUSION: The high expression of TGF-β/Smad/CTGF signaling pathway plays an important role in the pathogenesis of benign biliary stricture.

Keywords: Biliary stricture, Transforming growth factor-beta 1, Smad, Connective tissue growth factor, TβR