title: Posttranslational regulation of tissue inhibitor of metalloproteinase-1 by calcium-dependent vesicular exocytosis.
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.
authors.affiliation: Division of Gastroenterology & Hepatology, University of Arkansas for Medical Sciences Little Rock, Arkansas ; Research Service, Central Arkansas VA Healthcare System Little Rock, Arkansas.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Dranoff
authors.affiliation: Emory University Atlanta, Georgia.
authors.forename: Neal
authors.initials: N
authors.lastname: Bhatia
authors.affiliation: Division of Gastroenterology & Hepatology, University of Arkansas for Medical Sciences Little Rock, Arkansas ; Research Service, Central Arkansas VA Healthcare System Little Rock, Arkansas.
authors.forename: Michel
authors.initials: M
authors.lastname: Fausther
authors.affiliation: Division of Gastroenterology & Hepatology, University of Arkansas for Medical Sciences Little Rock, Arkansas ; Research Service, Central Arkansas VA Healthcare System Little Rock, Arkansas.
authors.forename: Elise G
authors.initials: EG
authors.lastname: Lavoie
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences Little Rock, Arkansas.
authors.forename: Susana
authors.initials: S
authors.lastname: Granell
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences Little Rock, Arkansas.
authors.forename: Giulia
authors.initials: G
authors.lastname: Baldini
authors.affiliation: Case Western Reserve University Cleveland, Ohio.
authors.forename: Dashawn A
authors.initials: DA
authors.lastname: Hickman
authors.affiliation: Platt Technical High School Milford, Connecticut.
authors.forename: Nina
authors.initials: N
authors.lastname: Sheung
keywords: Calcium; confocal microscopy; hepatic stellate cell; liver fibrosis