Coordinated expression of beta 1 integrins and transforming growth factor-beta-induced matrix proteins in glomerulonephritis.
Coordinated expression of beta 1 integrins and transforming growth factor-beta-induced matrix proteins in glomerulonephritis.
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发表时间：
1993-07
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通讯作者：
Shoji Kagami;W. A. Border;E. Ruoslahti;N. Noble
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作者：
Shoji Kagami;W. A. Border;E. Ruoslahti;N. Noble
背景组织损伤后的细胞外基质重塑涉及细胞与细胞和细胞与基质的相互作用。整合素是在这种相互作用中发挥核心作用的基质受体，而转化生长因子-β(TGF-β)被认为是其表达的强大调节器。我们以前的工作表明，在抗胸腺细胞血清诱导的大鼠肾小球肾炎模型中，肾小球转化生长因子-β的产生增加是基质积聚的一个原因。在此，我们介绍了在实验性肾小球肾炎中肾小球β1整合素的表达和分布。实验设计应用代谢标记、免疫组织化学和免疫沉淀技术，对正常大鼠和抗胸腺细胞血清诱导的大鼠肾小球肾炎过程中的肾小球进行研究。对含有β1亚基的整合素和作为这些整合素配体的细胞外基质成分的变化进行了表征。结果肾小球中α1、α5和β1亚单位的表达与肾小球系膜上α1β1和α5β1整合素、层粘连蛋白、胶原和纤维连接蛋白以及转化生长因子-β1蛋白的含量平行，发病第7天增加，第28天趋于正常。α3亚基则表现出相反的模式。外源性转化生长因子-β刺激正常肾小球合成α1β1和α5β1整合素，而不是其他细胞因子。结论数据表明，肾小球β1整合素的表达发生了改变，从而促进了细胞与已知在该疾病模型中积聚的基质蛋白的黏附。数据进一步表明，转化生长因子-β对这些变化负有责任。
BACKGROUND Extracellular matrix remodeling after tissue injury involves both cell-cell and cell-matrix interactions. Integrins are matrix receptors that play a central role in such interactions, and transforming growth factor-beta (TGF-beta) is known to be a strong modulator of their expression. Our previous work has shown that in the anti-thymocyte serum-induced model of glomerulonephritis in the rat, elevated glomerular production of TGF-beta is a causal factor in matrix accumulation. Here we present data on the expression and distribution of glomerular beta 1 integrins in experimental glomerulonephritis. EXPERIMENTAL DESIGN Metabolic labeling, immunohistochemical, and immunoprecipitation techniques were used on kidney glomeruli from normal rats and from rats over the course of glomerulonephritis induced by administration of anti-thymocyte serum. Changes in beta 1 subunit-containing integrins and the extracellular matrix components that serve as ligands for these integrins were characterized. RESULTS The data indicate that expression in glomeruli of alpha 1, alpha 5, and beta 1 subunits paralleled both mesangial content of the ligands for the alpha 1 beta 1 and alpha 5 beta 1 integrins, laminin, collagen and fibronectin, and TGF-beta 1 protein; increasing on day 7 of disease and decreasing toward normal by day 28. The alpha 3 subunit displayed the opposite pattern. Exogenous TGF-beta, but not other cytokines, stimulated synthesis of alpha 1 beta 1 and alpha 5 beta 1 integrins by normal glomeruli. CONCLUSIONS The data indicate that glomerular beta 1 integrin expression is altered in a manner that would promote cell adhesion to the matrix proteins known to accumulate in this disease model. The data further suggest that TGF-beta is responsible for these changes.