单核细胞趋化蛋白-1通过囊泡重新分布至大鼠门静脉成纤维细胞的溶酶体来下调基质金属蛋白酶-9的输出。
MCP-1 downregulates MMP-9 export via vesicular redistribution to lysosomes in rat portal fibroblasts.
作者信息
Hickman DaShawn A, Syal Gaurav, Fausther Michel, Lavoie Elise G, Goree Jessica R, Storrie Brian, Dranoff Jonathan A
机构信息
Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
出版信息
Physiol Rep. 2014 Nov 20;2(11). doi: 10.14814/phy2.12153. Print 2014 Nov 1.
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.
肝门成纤维细胞（PF）是构成肝脏肌成纤维细胞群的两种主要细胞类型之一，因此对肝纤维化的发病机制至关重要。单核细胞趋化蛋白-1（MCP-1）是一种已知的促纤维化趋化因子，在胆汁性纤维化中可能尤为重要。我们研究了MCP-1对大鼠PF释放基质金属蛋白酶-9（MMP-9）的影响。我们发现MCP-1以翻译后方式阻断PF释放MMP-9。我们采用光学和电子显微镜方法来确定这种下调的机制。我们的数据表明，在MCP-1存在的情况下，含MMP-9的囊泡被分流到溶酶体样区室。这是关于分泌蛋白在成纤维细胞中如此调控的首次报道。
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