The phenotypic modulation in renal arteriolar smooth muscles and the glomerular mesangial cells.

肾小动脉平滑肌和肾小球系膜细胞的表型调节。

基本信息

批准号：
05670949
负责人：
KIMURA Kenjiro
金额：
$ 1.34万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

In the present study we demonstrated that the phenotypic modulation occurred in smooth muscles of renal arterioles and in glomerular cells during development of hypertension and various glomerular diseases. Salt-loaded stroke-prone-spontaneously hypertensive rats (SHRSP) developed malignant hypertension. In the kidney, the expression of SM2 (muscle-type myosin heavy chain isoform) and alpha-actin was decreased according to the degree of vascular damages. As SM2 is regarded to be expressed in highly differentiated smooth muscles of strong contractility, the decrease in SM2 expression might result in functional abnormalities in arterioles, which accelerates hypertensive glomerular damage. The mesangial cells expressed non-muscle myosin, Smemb, and alpha-actin. In various glomerular diseases, the phenotypic modulation took place in the epithelial cells and in the mesangial cells. These phenotypic modulations were confirmed by the immunoelectron microscopy and also by the northern analysis of messenger RNA.In the anti-thy-1 glomerulonephritis, mesangial cells express alpha-actin from the earlier stage of the disease and also Smemb in the later stage. In the remnant kidney, Smemb was expressed in the mesangial cells at the earlier stage, but in the epithelial cells at the later stage, when the glomerular hypertrophy developed. In the anti-glomerular basement membrane glomerulonephritis and the streptozotocin-induced diabetic kidney, both the epithelial and mesangial cells expressed Smemb. In the remnant kidney, the anti-GBM glomerulonephritis or diabetic kidney, alpha-actin was not expressed at all. Thus, the phenotypic modulation of glomerular cells took place heterogeneously as well as in the varying manner. At present, the functional meaning of the phenotypic modulation of glomerular cells is unknown.

在本研究中，我们证明在高血压和各种肾小球疾病的发展过程中，表型调节发生在肾小动脉平滑肌和肾小球细胞中。含盐的易发生中风的自发性高血压大鼠（SHRSP）出现恶性高血压。在肾脏中，SM2（肌肉型肌球蛋白重链亚型）和α-肌动蛋白的表达根据血管损伤的程度而降低。由于SM2被认为在高度分化、收缩力强的平滑肌中表达，SM2表达减少可能导致小动脉功能异常，从而加速高血压肾小球损伤。系膜细胞表达非肌肉肌球蛋白、Smemb 和 α-肌动蛋白。在各种肾小球疾病中，表型调节发生在上皮细胞和系膜细胞中。这些表型调节通过免疫电镜和信使 RNA 的 Northern 分析得到证实。在抗 thy-1 肾小球肾炎中，系膜细胞在疾病早期表达 α-肌动蛋白，在疾病后期也表达 Smemb。在残肾中，Smemb早期表达于系膜细胞，后期肾小球肥大时表达于上皮细胞。在抗肾小球基底膜肾炎和链脲佐菌素诱导的糖尿病肾中，上皮细胞和系膜细胞均表达Smemb。在残余肾、抗GBM肾小球肾炎或糖尿病肾中，α-肌动蛋白根本不表达。因此，肾小球细胞的表型调节以不同的方式异质地发生。目前，肾小球细胞表型调节的功能意义尚不清楚。