title: Upregulation of EMMPRIN after permanent focal cerebral ischemia.
abstract: Elevated activities of matrix metalloproteinases (MMPs) following ischemic stroke have been shown to mediate ischemic injury as well as neurovascular remodeling. The extracellular MMP inducer (EMMPRIN) is a 58-kDa cell surface glycoprotein, which has been known to play a key regulatory role for MMP activities. The roles of EMMPRIN in stroke injury are not clearly understood. In this study, we investigated changes of EMMPRIN in a mouse model of permanent focal cerebral ischemia, and examined potential association between EMMPRIN and MMP-9 expression. Adult male CD-1 mice were subjected to permanent focal ischemia by intraluminal occlusion of the left middle cerebral artery (MCAO) under anesthesia. EMMPRIN expression was markedly upregulated in the peri-infarct area at 2-7 days after ischemia compared to the contralateral non-ischemic hemisphere by Western blot analysis. Immunofluorescent double staining demonstrated that EMMPRIN signals co-localized with vwF-positive endothelial cells and GFAP-positive peri-vascular astrocytes. In contrast, EMMPRIN signal did not co-localize with NeuN-positive neurons, or MPO-positive neutrophils. Dual fluorescent staining revealed that EMMPRIN co-localized with MMP-9. Our data also demonstrated that increased EMMPRIN expression correlated with increased MMP-9 levels in a temporal manner. In summary, we report for the first time that EMMPRIN expression was significantly increased in a mouse model of permanent focal cerebral ischemia. The spatial and temporal association between increased EMMPRIN expression and elevated MMP-9 levels suggest that EMMPRIN may modulate MMP-9 activity, and participate in neurovascular remodeling after ischemic stroke.
authors.affiliation: Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Steve
authors.initials: S
authors.lastname: Khachi
authors.forename: Qi
authors.initials: Q
authors.lastname: Hao
authors.forename: Fanxia
authors.initials: F
authors.lastname: Shen
authors.forename: William L
authors.initials: WL
authors.lastname: Young
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Yang
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D051926:Basigin / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D020520:Brain Infarction / Q000378:metabolism* / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D051379:Mice; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C497887:Bsg protein, mouse; D005904:Glial Fibrillary Acidic Protein; D010980:Platelet Membrane Glycoproteins; C028254:von Willebrand factor receptor; D051926:Basigin; D020780:Matrix Metalloproteinase 9