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，我们证明了表型调节发生在高血压和各种肾小球疾病的发育过程中肾动脉和肾小球细胞的平滑肌中发生。盐负载的雌性易于发作的高血压大鼠（SHRSP）出现恶性高血压。在肾脏中，根据血管损伤程度降低了SM2（肌肉肌球蛋白重链同工型）和α-肌动蛋白的表达。由于SM2被认为在高度分化的平滑肌肉中表达，因此SM2表达的降低可能导致小动脉的功能异常，从而加速了高血压肾小球损伤。肾小球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膜细胞中。这些表型调节通过免疫电子显微镜以及信信体RNA的北部分析证实了这些表型调节。在抗THY-1肾小球肾炎中，膜细胞从疾病的早期阶段表达α-肌动蛋白，并在后期smemb。在残留肾脏中，SMEMB在早期的肾小球细胞中表达，但是在后期的上皮细胞中，肾小球肥大出现了。在抗斜体基底膜肾小球肾炎和链蛋白酶诱导的糖尿病性肾脏中，上皮细胞和肾小球细胞都表达了Smemb。在残留肾脏中，抗GBM肾小球肾炎或糖尿病性肾脏，根本没有表达α-肌动蛋白。因此，肾小球细胞的表型调节是异质和不同方式发生的。目前，肾小球细胞表型调节的功能含义尚不清楚。