EXPRESSION OF SMOOTH-MUSCLE CELL PHENOTYPE BY RAT MESANGIAL CELLS IN IMMUNE-COMPLEX NEPHRITIS - ALPHA-SMOOTH MUSCLE ACTIN IS A MARKER OF MESANGIAL CELL-PROLIFERATION
EXPRESSION OF SMOOTH-MUSCLE CELL PHENOTYPE BY RAT MESANGIAL CELLS IN IMMUNE-COMPLEX NEPHRITIS - ALPHA-SMOOTH MUSCLE ACTIN IS A MARKER OF MESANGIAL CELL-PROLIFERATION
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DOI：
10.1172/jci115089
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发表时间：
1991-03-01
影响因子：
15.9
通讯作者：
GOWN, AM
中科院分区：
文献类型：
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作者：
JOHNSON, RJ;IIDA, H;GOWN, AM
肾小球系膜细胞增殖在肾小球肾炎中很常见，但尚不清楚增殖是否与体内表型改变有关。我们研究了是否系膜细胞获得平滑肌样特征的系膜增生性肾炎的大鼠模型诱导的抗体的Thy-1抗原存在于系膜细胞。在第3天，肾小球显示新生免疫染色的α-平滑肌肌动蛋白的系膜模式，与增殖的开始，并持续到第14天。结蛋白和波形蛋白在系膜区也有增加。免疫电镜证实肌动蛋白阳性细胞为系膜细胞，免疫双标记显示平滑肌肌动蛋白阳性细胞增殖活跃。分离的肾小球RNA的北方分析证实在第3天和第5天α和β/γ-肌动蛋白mRNA增加。补体耗竭或血小板耗竭分别阻止或减少增殖;这些操作也阻止了平滑肌肌动蛋白和肌动蛋白基因表达。对其他五种肾炎实验模型的研究证实，平滑肌肌动蛋白表达是系膜细胞损伤的标志。因此，大鼠肾小球肾炎中的系膜细胞增殖与系膜细胞呈现平滑肌细胞特征的明显表型变化相关。
Mesangial cell proliferation is common in glomerulonephritis but it is unclear if proliferation is associated with any in vivo alteration in phenotype. We investigated whether mesangial cells acquire smooth muscle-like characteristics in a rat model of mesangial proliferative nephritis induced with antibody to the Thy-1 antigen present on mesangial cells. At day 3 glomeruli displayed de novo immunostaining for alpha-smooth muscle actin in a mesangial pattern, correlating with the onset of proliferation, and persisting until day 14. An increase in desmin and vimentin in mesangial regions was also noted. Immunoelectron microscopy confirmed that the actin-positive cells were mesangial cells, and double immunolabeling demonstrated that the smooth muscle actin-positive cells were actively proliferating. Northern analysis of isolated glomerular RNA confirmed an increase in alpha and beta/gamma-actin mRNA at days 3 and 5. Complement depletion or platelet depletion prevented or reduced proliferation, respectively; these maneuvers also prevented smooth muscle actin and actin gene expression. Studies of five other experimental models of nephritis confirmed that smooth muscle actin expression is a marker for mesangial cell injury. Thus, mesangial cell proliferation in glomerulonephritis in the rat is associated with a distinct phenotypic change in which mesangial cells assume smooth muscle cell characteristics.