Protection of cerulein-induced pancreatic fibrosis by pancreas-specific expression of Smad7.
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 I 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.
He
Jing
J
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, China.
Sun
Xiaolan
X
Qian
Ke-Qing
KQ
Liu
Xubao
X
Wang
Zhenzhen
Z
Chen
Yan
Y
D000199:Actins / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002108:Ceruletide / Q000633:toxicity; D024042:Collagen Type I / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D015870:Gene Expression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009928:Organ Specificity; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D000199:Actins; D024042:Collagen Type I; D017931:DNA Primers; D005353:Fibronectins; D011994:Recombinant Proteins; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; D002108:Ceruletide