Posttranslational regulation of tissue inhibitor of metalloproteinase‐1 by calcium‐dependent vesicular exocytosis

Physiological Reports

Jonathan A. Dranoff²  Neal Bhatia³  Michel Fausther²  Elise G. Lavoie²  Susana Granell¹  Giulia Baldini¹  DaShawn A. Hickman⁴ 

[1] Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas;Division of Gastroenterology & Hepatology, University of Arkansas for Medical Sciences, Little Rock, Arkansas;Emory University, Atlanta, Georgia;Case Western Reserve University, Cleveland, Ohio

关键词: Calcium;    confocal microscopy;    hepatic stellate cell;    liver fibrosis;   

DOI  :  10.1002/phy2.125

来源: Wiley

【 摘 要 】

Abstract

Liver myofibroblasts derived from hepatic stellate cells (HSC) are critical mediators of liver fibrosis. Release of tissue inhibitor of metalloproteinase-1 (TIMP-1) advances liver fibrosis by blocking fibrinolysis. The mechanisms responsible for the posttranslational regulation of TIMP-1 by myofibroblastic HSC are unknown. Here, we demonstrate that TIMP-1 release by HSC is regulated in a posttranslational fashion via calcium-sensitive vesicular exocytosis. To our knowledge, this is the first article to directly examine vesicular trafficking in myofibroblastic HSC, potentially providing a new target to treat and or prevent liver fibrosis.

【 授权许可】

CC BY   
© 2013 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.