The uPA/uPAR system in astrocytic wound healing  

作　　者：Manuel Yepes 

机构地区：[1]Division of Neuropharmacology and Neurologic Diseases,Yerkes National Primate Research Center,Atlanta,GA,USA [2]Department of Neurology,Emory University School of Medicine,Atlanta,GA,USA [3]Department of Neurology,Veterans Affairs Medical Center,Atlanta,GA,USA

出　　处：《Neural Regeneration Research》2022年第11期2404-2406,共3页中国神经再生研究（英文版）

基　　金：National Institutes of Health Grant NS-091201(to MY);VA MERIT Award I01BX003441(to MY)。

摘　　要：The repair of injured tissue is a highly complex process that involves cell prolife ration,differentiation,and migration.Cell migration requires the dismantling of intercellular contacts in the injured zone and their subsequent reconstitution in the wounded area.Urokinase-type plasminogen activator(u PA)is a serine proteinase found in multiple cell types including endothelial cells,smooth muscle cells,monocytes,and macrophages.A substantial body of experimental evidence with different cell types outside the central nervous system indicates that the binding of uPA to its receptor(uPAR)on the cell surface prompts cell migration by inducing plasmin-mediated degradation of the extracellular matrix.In contrast,although uPA and uPAR are abundantly found in astrocytes and u PA binding to uPAR triggers astrocytic activation,it is unknown if uPA also plays a role in astrocytic migration.Neuronal cadherin is a member of cell adhesion proteins pivotal for the formation of cell-cell conta cts between astrocytes.More specifically,while the extracellular domain of neuronal cadherin interacts with the extracellular domain of neuronal cadherin in neighboring cells,its intracellular domain binds toβ-catenin,which in turn links the complex to the actin cytos keleton.Glycogen synthase kinase 3βis a serine-threonine kinase that prevents the cytoplasmic accumulation ofβ-catenin by inducing its phosphorylation at Ser33,Ser37,and Ser41,thus activating a sequence of events that lead to its proteasomal degradation.The data discussed in this perspective indicate that astrocytes release u PA following a mechanical injury,and that binding of this u PA to uPAR on the cell membrane induces the detachment ofβ-catenin from the intracellular domain of neuronal cadherin by triggering its extracellular signal-regulated kinase 1/2-mediated phosphorylation at Tyr650.Remarkably,this is followed by the cytoplasmic accumulation ofβ-catenin because uPA-induced extracellular signalregulated kinase 1/2 activation also phosphorylates lipoprotein recep

关 键 词：ASTROCYTES lipoprotein receptor-related protein 6 PLASMIN urokinase receptor urokinase-type plasminogen activator Wnt-β-catenin pathway wound healing Β-CATENIN 

分 类 号：R741[医药卫生—神经病学与精神病学]