Background. Glomerular mesangial cell (MC) proliferation, hypertrophy, and
abnormal matrix remodeling characterized hv increased expression of fibrone
ctin, laminin and collagen type IV, and neoexpression of collagen I and III
are the main biological features of progressive glomerulonephritis (GN). E
specially, persistent pathological matrix remodeling may lead to glomerular
scar formation (glomerular scarring). We reported recently that alpha(1)be
ta(1) integrin, a major collagen receptor for MCs, may be a potential adhes
ion molecule for MC-mediated pathological collagen matrix remodeling in GN.
Methods. To address further the direct role of alpha(1)beta(1) integrin in
MC behavior, such as cell growth and matrix remodeling, alpha(1)beta(1) int
egrin was overexpressed in MCs by transfecting an expression vector contain
ing a full-length rat alpha(1) integrin cDNA. Flow cytometry and immunoprec
ipitation analysis were applied for selection of transfectants with a stabl
e expression of the alpha(1) integrin subunit. The effect alpha(1)beta(1) i
ntegrin overexpression on MC: biology was examined with a H-3-thymidine inc
orporation assay, Row cytometric analysis of cell size and DNA content, Wes
tern blot analysis of a cyclin-dependent-kinase inhibitor, p27(Kip1), alpha
-smooth muscle actin expression, and a collagen gel contraction assay.
Results. The oil transfectants displayed a dramatic inhibition of H-3-thymi
dine incorporation as compared with the mock transfectants. Increased expre
ssion of the oil subunit inversely correlated with cell cycle progression a
nd paralleled the expression of p27(Kip1) and alpha-smooth muscle actin, as
well as the cell size in MCs. In addition, the alpha(1)-transfectants were
able to enhance collagen matrix reorganization effectively.
Conclusion. These results indicate that MC-alpha(1)beta(1) integrin express
ion is a critical determinant of MC phenotypes, including cell growth, cell
size, and collagen matrix remodeling ability, and thereby contributes to s
car matrix remodeling (sclerosis) in GN.