Open AccessPosttranslational regulation of tissue inhibitor of metalloproteinase‐1 by calcium‐dependent vesicular exocytosis
Author(s) -
Dranoff Jonathan A.,
Bhatia Neal,
Fausther Michel,
Lavoie Elise G.,
Granell Susana,
Baldini Giulia,
Hickman DaShawn A.,
Sheung Nina
Publication year - 2013
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.1002/phy2.125
Subject(s) - exocytosis , hepatic stellate cell , microbiology and biotechnology , myofibroblast , metalloproteinase , tissue inhibitor of metalloproteinase , matrix metalloproteinase , fibrosis , chemistry , biology , pathology , medicine , extracellular matrix , biochemistry , secretion
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.