Protection of cerulein-induced pancreatic fibrosis by pancreas-specific expression of Smad7

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1792

Article

He, Jing¹  Sun, Xiaolan¹  Qian, Ke-Qing²  Liu, Xubao³  Wang, Zhenzhen¹  Chen, Yan¹ 

[1] Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai 200031, Peoples R China

[2] Nanjing Med Univ, Changzhou Peoples Hosp 2, Dept Oncol, Changzhou, Jiangsu, Peoples R China

[3] Sichuan Univ, W China Hosp, Dept Surg, Chengdu 610064, Peoples R China

关键词: Chronic pancreatitis;    Fibrosis;    Smad7;    TGF-beta;    Transgenic mouse;   

DOI  :  10.1016/j.bbadis.2008.10.010

来源: Elsevier

【 摘 要 】

Pancreatic fibrosis is the hallmark of chronic pancreatitis, currently an incurable disease. Pancreatitis fibrosis is caused by deposition of extracellular matrix (ECM) and the underlying pathological mechanism remains unclear. In addition to its broad biological activities, TGF-beta is a potent pro-fibrotic factor and many in vitro studies using cell systems have implicated a functional role of TGF-beta in the pathogenesis of pancreatic fibrosis. We analyzed the in vivo role of TGF-beta pathway in pancreatic fibrosis in this study. Smad7, an intracellular inhibitory protein that antagonizes TGF-beta signaling, was specifically expressed in the pancreas using a transgenic mouse model. Chronic pancreatitis was induced in the mouse with repeated administration of cerulein. Smad7 expression in the pancreas was able to significantly inhibit cerulein-induced pancreatic fibrosis. Consistently, the protein levels of collagen 1 and fibronectin were decreased in the Smad7 transgenic mice. In addition, alpha-smooth muscle actin, a marker of activated pancreas stellate cells, was reduced in the transgenic mice. Taken together, these data indicate that inhibition of TGF-beta signaling by Smad7 is able to protect cerulein-induced pancreatic fibrosis in vivo. (C) 2008 Elsevier B.V. All rights reserved.

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