Overexpression of alpha(1)beta(1) integrin directly affects rat mesangial cell behavior

Citation
S. Kagami et al., Overexpression of alpha(1)beta(1) integrin directly affects rat mesangial cell behavior, KIDNEY INT, 58(3), 2000, pp. 1088-1097
Citations number
48
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Urology & Nephrology","da verificare
Journal title
KIDNEY INTERNATIONAL
ISSN journal
0085-2538 → ACNP
Volume
58
Issue
3
Year of publication
2000
Pages
1088 - 1097
Database
ISI
SICI code
0085-2538(200009)58:3<1088:OOAIDA>2.0.ZU;2-W
Abstract
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.