EXPRESSION OF A NONMUSCLE MYOSIN HEAVY-CHAIN IN GLOMERULAR CELLS DIFFERENTIATES VARIOUS TYPES OF GLOMERULAR-DISEASE IN RATS

To characterize the phenotypic modulation of mesangial and glomerular epithelial cells, we investigated the expression of a nonmuscle type m yosin heavy chain, SMemb, and alpha-smooth muscle actin (alpha-SM acti n) in rat experimental glomerular diseases, which included anti-Thy 1 nephritis, 5/6 nephrectomy, diabetes, and anti-glomerular basement mem brane nephritis. SMemb was only slightly expressed in normal glomerula r epithelial cells but not in mesangial cells. In the anti-Thy 1 nephr itis rats, both SMemb and alpha-SM actin were most conspicuously induc ed in mesangial cells. However, the expression profile was shifted fro m alpha-SM actin to SMemb dominant pattern over the course of glomerul onephritis. The expression of SMemb was also increased in epithelial c ells in this model. In the other three models, glomerular cells did no t 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 epithel ial cells when severe glomerular hypertrophy developed. In the anti-GE M nephritis rats, SMemb expression was increased in epithelial cells. In all models examined, mesangial and epithelial expression of SMemb w as confirmed by immunoelectron microscopy, and enhanced expression of SMemb mRNA in glomeruli was verified by RNase protection assay. We con clude 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 usef ul to detect both mesangial and glomerular epithelial cell activation in these glomerular disease models. Understanding the functional diffe rence and regulatory mechanisms of these cytoskeletal proteins will pr ovide insight into the pathogenesis and progression of glomerular dise ases.