biostudies-literatureDranoff JAYale Liver CenterNIDDK NIH HHSNational Institutes of HealthNIDDKe00125https://www.ebi.ac.uk/biostudies/studies/S-EPMC3871447biostudies-literatureUnknown1(6)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.Physiological reportsPosttranslational regulation of tissue inhibitor of metalloproteinase-1 by calcium-dependent vesicular exocytosis.PMC3871447DK45710DK076735R01 DK076735Bhatia NDranoff JAFausther MBaldini GGranell SLavoie EGSheung NHickman DAfalsePosttranslational regulation of tissue inhibitor of metalloproteinase-1 by calcium-dependent vesicular exocytosis.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.2013-01-01T00:00:00Z2013 Nov2025-04-22T01:14:04.323Z2019-03-27T01:18:56ZS-EPMC38714472440013410.1002/phy2.125