title: MCP-1 downregulates MMP-9 export via vesicular redistribution to lysosomes in rat portal fibroblasts.
abstract: Portal fibroblasts (PF) are one of the two primary cell types contributing to the myofibroblast population of the liver and are thus essential to the pathogenesis of liver fibrosis. Monocyte chemoattractant protein-1 (MCP-1) is a known profibrogenic chemokine that may be of particular importance in biliary fibrosis. We examined the effect of MCP-1 on release of matrix metalloproteinase-9 (MMP-9) by rat PF. We found that MCP-1 blocks PF release of MMP-9 in a posttranslational fashion. We employed an optical and electron microscopic approach to determine the mechanism of this downregulation. Our data demonstrated that, in the presence of MCP-1, MMP-9-containing vesicles were shunted to a lysosome-like compartment. This is the first report of a secretory protein to be so regulated in fibrogenic cells.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: DaShawn A
authors.initials: DA
authors.lastname: Hickman
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Syal
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Michel
authors.initials: M
authors.lastname: Fausther
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Elise G
authors.initials: EG
authors.lastname: Lavoie
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Goree
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Brian
authors.initials: B
authors.lastname: Storrie
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Dranoff
keywords: Lysosome; MCP‐1; MMP‐9; portal fibroblast