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 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.
Hiroi
J
J
Third Department of Internal Medicine, University of Tokyo, Japan.
Kimura
K
K
Aikawa
M
M
Tojo
A
A
Suzuki
Y
Y
Nagamatsu
T
T
Omata
M
M
Yazaki
Y
Y
Nagai
R
R
D000199:Actins / Q000378:metabolism; D000818:Animals; D001485:Basement Membrane / Q000276:immunology; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016253:Microscopy, Immunoelectron; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D009392:Nephrectomy; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018800:Thy-1 Antigens
D000199:Actins; D012333:RNA, Messenger; D018800:Thy-1 Antigens; D018995:Myosin Heavy Chains