PMID- 25413315 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20141121 LR - 20181113 IS - 2051-817X (Print) IS - 2051-817X (Electronic) IS - 2051-817X (Linking) VI - 2 IP - 11 DP - 2014 Nov 1 TI - MCP-1 downregulates MMP-9 export via vesicular redistribution to lysosomes in rat portal fibroblasts. LID - 10.14814/phy2.12153 [doi] LID - e12153 AB - 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. CI - (c) 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society. FAU - Hickman, DaShawn A AU - Hickman DA AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas. FAU - Syal, Gaurav AU - Syal G AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas. FAU - Fausther, Michel AU - Fausther M AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas. FAU - Lavoie, Elise G AU - Lavoie EG AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas. FAU - Goree, Jessica R AU - Goree JR AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas. FAU - Storrie, Brian AU - Storrie B AD - Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas. FAU - Dranoff, Jonathan A AU - Dranoff JA AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas. LA - eng PT - Journal Article DEP - 20141120 PL - United States TA - Physiol Rep JT - Physiological reports JID - 101607800 PMC - PMC4255798 OTO - NOTNLM OT - Lysosome OT - MCP-1 OT - MMP-9 OT - portal fibroblast EDAT- 2014/11/22 06:00 MHDA- 2014/11/22 06:01 PMCR- 2014/11/20 CRDT- 2014/11/22 06:00 PHST- 2014/11/22 06:00 [entrez] PHST- 2014/11/22 06:00 [pubmed] PHST- 2014/11/22 06:01 [medline] PHST- 2014/11/20 00:00 [pmc-release] AID - 2/11/e12153 [pii] AID - phy212153 [pii] AID - 10.14814/phy2.12153 [doi] PST - epublish SO - Physiol Rep. 2014 Nov 20;2(11):e12153. doi: 10.14814/phy2.12153. Print 2014 Nov 1.