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Role of TGF-β1 in the development of pancreatic fibrosis in Otsuka Long-Evans Tokushima Fatty rats

Role of TGF-β1 in the development of pancreatic fibrosis in Otsuka Long-Evans Tokushima Fatty rats Abstract Recently established Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of naturally occurring obesity diabetes, exhibit progressive accumulation of connective tissue in the pancreas. The present study was designed to determine the pathogenic role of transforming growth factor-β1 (TGF-β1) in the development of pancreatic fibrosis in OLETF rats by investigating the serial changes in the expression of TGF-β1 and extracellular matrix (ECM) in the pancreas. Progressive proliferation of connective tissue arose from the interstitial region surrounding islets at 20 wk of age and extended to the exocrine pancreas adjacent to the islets. TGF-β1 mRNA levels in the pancreas increased at 20 wk of age and reached a peak value at 30 wk of age. Fibronectin (FN) and procollagen types I and III mRNAs peaked at 20 wk of age and remained at higher levels than those in the nondiabetic counterparts Long-Evans Tokushima Otsuka rats until 50 wk of age. Immunoreactivities for TGF-β1 and FN were found in islets of OLETF rats at 20 wk of age and were seen in acinar and interstitial cells at 50 wk of age. Moreover, α-smooth muscle actin was located at interstitial region surrounding the islets. Proliferation of the connective tissue in the pancreas of OLETF rats closely correlated with expression of TGF-β1 and ECM. Our results suggest that the development of pancreatic fibrosis in OLETF rats extends from endocrine to exocrine pancreas and that TGF-β1 is involved in pancreatic fibrosis of OLETF rats. extracellular matrix myofibroblast Type 2 diabetes pancreatic stellate cell transforming growth factor-β1 Footnotes Address for reprint requests and other correspondence: M. Otsuki, Third Dept. of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, 1–1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807–8555 Japan (E-mail: mac-otsk@med.uoeh-u.ac.jp ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 10.1152/ajpgi.00323.2001 Copyright © 2002 the American Physiological Society http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png AJP - Gastrointestinal and Liver Physiology The American Physiological Society

Role of TGF-β1 in the development of pancreatic fibrosis in Otsuka Long-Evans Tokushima Fatty rats

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Publisher
The American Physiological Society
Copyright
Copyright © 2011 the American Physiological Society
ISSN
0193-1857
eISSN
1522-1547
DOI
10.1152/ajpgi.00323.2001
pmid
11842006
Publisher site
See Article on Publisher Site

Abstract

Abstract Recently established Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of naturally occurring obesity diabetes, exhibit progressive accumulation of connective tissue in the pancreas. The present study was designed to determine the pathogenic role of transforming growth factor-β1 (TGF-β1) in the development of pancreatic fibrosis in OLETF rats by investigating the serial changes in the expression of TGF-β1 and extracellular matrix (ECM) in the pancreas. Progressive proliferation of connective tissue arose from the interstitial region surrounding islets at 20 wk of age and extended to the exocrine pancreas adjacent to the islets. TGF-β1 mRNA levels in the pancreas increased at 20 wk of age and reached a peak value at 30 wk of age. Fibronectin (FN) and procollagen types I and III mRNAs peaked at 20 wk of age and remained at higher levels than those in the nondiabetic counterparts Long-Evans Tokushima Otsuka rats until 50 wk of age. Immunoreactivities for TGF-β1 and FN were found in islets of OLETF rats at 20 wk of age and were seen in acinar and interstitial cells at 50 wk of age. Moreover, α-smooth muscle actin was located at interstitial region surrounding the islets. Proliferation of the connective tissue in the pancreas of OLETF rats closely correlated with expression of TGF-β1 and ECM. Our results suggest that the development of pancreatic fibrosis in OLETF rats extends from endocrine to exocrine pancreas and that TGF-β1 is involved in pancreatic fibrosis of OLETF rats. extracellular matrix myofibroblast Type 2 diabetes pancreatic stellate cell transforming growth factor-β1 Footnotes Address for reprint requests and other correspondence: M. Otsuki, Third Dept. of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, 1–1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807–8555 Japan (E-mail: mac-otsk@med.uoeh-u.ac.jp ). The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “ advertisement ” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 10.1152/ajpgi.00323.2001 Copyright © 2002 the American Physiological Society

Journal

AJP - Gastrointestinal and Liver PhysiologyThe American Physiological Society

Published: Mar 1, 2002

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