Hypertensive glomerular damage as revealed by the expression of alpha-smooth muscle actin and non-muscle myosin.
The aim of this study was to determine the phenotypic modulation in mesangial cells of glomeruli damaged by hypertension. Salt-loaded stroke-prone spontaneously hypertensive rats were untreated or treated with a calcium antagonist, manidipine (2 mg/kg/day) for eight weeks. In normotensive Wistar-Kyoto rats, alpha-smooth muscle actin was not expressed in any glomerular cells and a non-muscle myosin heavy chain isoform, SMemb, was slightly expressed in glomerular visceral epithelial cells. In the untreated hypertensive rats, the glomeruli showed sclerosis to various degrees and expressed alpha-smooth muscle actin and SMemb. Normal expression of SMemb in the epithelial cells disappeared. Notably, alpha-smooth muscle actin-positive fibroblast-like cells appeared in the interstitium, especially around the Bowman's capsules. Manidipine ameliorated the glomerulosclerosis and reduced the expression of alpha-smooth muscle actin in mesangial cells. In conclusion, the mesangial cells changed their phenotypes and expressed alpha-smooth muscle actin and SMemb in the glomeruli during the development of hypertensive renal damage. These phenotypically changed mesangial cells are considered to be activated and to produce various kinds of cytokines and extracellular matrix, which leads to glomerulosclerosis. Manidipine attenuated the glomerular damage and the phenotypic changes. The functional relevance of phenotypic changes in these cells should be elucidated in future studies.
Kimura
K
K
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Suzuki
N
N
Ohba
S
S
Nagai
R
R
Hiroi
J
J
Mise
N
N
Tojo
A
A
Nagaoka
A
A
Hirata
Y
Y
Goto
A
A
Yazaki
Y
Y
Omata
M
M
D000199:Actins / Q000096:biosynthesis*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005920:Glomerular Mesangium / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism*; D009218:Myosins / Q000096:biosynthesis*; D010641:Phenotype; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000199:Actins; D009218:Myosins