Barnes J L, Mitchell R J, Torres E S
Department of Medicine, University of Texas Health Science Center, San Antonio 78284, USA.
J Histochem Cytochem. 1995 Sep;43(9):895-905. doi: 10.1177/43.9.7642963.
Pericellular proteolysis involves the plasminogen activator/plasmin system and plays an important role in cell remodeling involving cell migration and extracellular matrix turnover. Studies in this laboratory have previously characterized a model of proliferative glomerulonephritis induced by Habu snake venom (HSV) in the rat that involves cell migration, proliferation, and extracellular matrix accumulation. Because plasminogen activator-inhibitor-1 (PAI-1) has been used as a marker for cell migration as well as matrix accumulation, we were interested in examining the temporal and spatial expression and cellular sources of PAI-1 mRNA and translated protein over the course of HSV-induced proliferative glomerulonephritis. The results showed a highly localized and progressive expression of PAI-1 mRNA and translated protein by in situ hybridization and immunohistochemistry at the margins and periphery of glomerular lesions 8 and 24 hr after HSV. The expression of PAI-1 in glomerular lesions localized to the same sites as mesangial cell marker proteins, desmin and Thy-1.1, indicating that mesangial cells synthesize this important regulator proteolysis. Few cells expressed PAI-1 in the central aspects of glomerular lesions at later time intervals (48 and 72 hr) when cell proliferation and expression of extracellular matrix (fibronectin protein and mRNA) were maximal. Therefore, the expression of PAI-1 in this model was associated more with early events related to cell migration than with proliferation or extracellular matrix synthesis. These observations support the hypothesis that the plasminogen activator/plasmin system is involved in cell migration in early remodeling during glomerular disease.
细胞周围蛋白水解作用涉及纤溶酶原激活物/纤溶酶系统，并在涉及细胞迁移和细胞外基质更新的细胞重塑过程中发挥重要作用。本实验室先前的研究已经对大鼠中由蝮蛇毒（HSV）诱导的增殖性肾小球肾炎模型进行了特征描述，该模型涉及细胞迁移、增殖和细胞外基质积累。由于纤溶酶原激活物抑制剂-1（PAI-1）已被用作细胞迁移以及基质积累的标志物，我们有兴趣研究在HSV诱导的增殖性肾小球肾炎过程中PAI-1 mRNA和翻译蛋白的时空表达及细胞来源。结果显示，通过原位杂交和免疫组织化学法，在HSV注射后8小时和24小时，肾小球病变边缘和周边区域PAI-1 mRNA和翻译蛋白呈现高度局部化且渐进性的表达。肾小球病变中PAI-1的表达定位于与系膜细胞标志物蛋白、结蛋白和Thy-1.1相同的部位，表明系膜细胞合成这种重要的调节蛋白水解作用的物质。在后期（48小时和72小时），当细胞增殖和细胞外基质（纤连蛋白蛋白和mRNA）表达达到最大值时，肾小球病变中心区域很少有细胞表达PAI-1。因此，该模型中PAI-1的表达更多地与细胞迁移相关的早期事件有关，而非与增殖或细胞外基质合成有关。这些观察结果支持了纤溶酶原激活物/纤溶酶系统参与肾小球疾病早期重塑过程中细胞迁移的假说。
