Hiroi J, Kimura K, Aikawa M, Tojo A, Suzuki Y, Nagamatsu T, Omata M, Yazaki Y, Nagai R
Third Department of Internal Medicine, University of Tokyo, Japan.
Kidney Int. 1996 May;49(5):1231-41. doi: 10.1038/ki.1996.177.
To characterize the phenotypic modulation of mesangial and glomerular epithelial cells, we investigated the expression of a nonmuscle type myosin heavy chain, SMemb, and alpha-smooth muscle actin (alpha-SM actin) in rat experimental glomerular diseases, which included anti-Thy 1 nephritis, 5/6 nephrectomy, diabetes, and anti-glomerular basement membrane nephritis. SMemb was only slightly expressed in normal glomerular epithelial cells but not in mesangial cells. In the anti-Thy 1 nephritis rats, both SMemb and alpha-SM actin were most conspicuously induced in mesangial cells. However, the expression profile was shifted from alpha-SM actin to SMemb dominant pattern over the course of glomerulonephritis. The expression of SMemb was also increased in epithelial cells in this model. In the other three models, glomerular cells did not express alpha-SM actin, but did so for SMemb. In the nephrectomized and the diabetic rats SMemb was newly expressed in mesangial cells at earlier stages, but at later stages was remarkably enhanced in epithelial cells when severe glomerular hypertrophy developed. In the anti-GBM nephritis rats, SMemb expression was increased in epithelial cells. In all models examined, mesangial and epithelial expression of SMemb was confirmed by immunoelectron microscopy, and enhanced expression of SMemb mRNA in glomeruli was verified by RNase protection assay. We conclude from these results that glomerular cells change their phenotypes differently depending on various types of glomerular diseases. These phenotypic changes in glomerular cells can be revealed by the combined immunostaining for SMemb and alpha-SM actin. SMemb is especially useful to detect both mesangial and glomerular epithelial cell activation in these glomerular disease models. Understanding the functional difference and regulatory mechanisms of these cytoskeletal proteins will provide insight into the pathogenesis and progression of glomerular diseases.
为了表征系膜细胞和肾小球上皮细胞的表型调节，我们研究了非肌肉型肌球蛋白重链SMemb和α-平滑肌肌动蛋白（α-SM肌动蛋白）在大鼠实验性肾小球疾病中的表达，这些疾病包括抗Thy 1肾炎、5/6肾切除、糖尿病和抗肾小球基底膜肾炎。SMemb在正常肾小球上皮细胞中仅轻微表达，而在系膜细胞中不表达。在抗Thy 1肾炎大鼠中，系膜细胞中SMemb和α-SM肌动蛋白均最显著地被诱导。然而，在肾小球肾炎过程中，表达谱从α-SM肌动蛋白转变为以SMemb为主的模式。在该模型中，上皮细胞中SMemb的表达也增加。在其他三种模型中，肾小球细胞不表达α-SM肌动蛋白，但表达SMemb。在肾切除和糖尿病大鼠中，系膜细胞在早期新表达SMemb，但在后期，当严重的肾小球肥大发展时，上皮细胞中SMemb显著增强。在抗GBM肾炎大鼠中，上皮细胞中SMemb表达增加。在所有检测的模型中，通过免疫电子显微镜证实了系膜和上皮细胞中SMemb的表达，并通过核糖核酸酶保护试验验证了肾小球中SMemb mRNA的表达增强。从这些结果我们得出结论，肾小球细胞根据不同类型的肾小球疾病而不同地改变其表型。肾小球细胞中的这些表型变化可以通过对SMemb和α-SM肌动蛋白的联合免疫染色来揭示。SMemb对于检测这些肾小球疾病模型中的系膜和肾小球上皮细胞激活特别有用。了解这些细胞骨架蛋白的功能差异和调节机制将有助于深入了解肾小球疾病的发病机制和进展。
