Adhesion of rat glomerular epithelial cells to extracellular matrices: Role of β1 integrins

Abstract

Glomerular epithelial cells (GEC) maintain glomerular permselectivity and are a target of immunological glomerular injury, which may lead to proliferation or detachment from extracellular matrix (ECM). We studied adhesion mechanisms in rat GEC in culture, focusing on adhesion molecules of the beta 1 integrin family. At early time points (1 hr after plating of cells into culture wells that had been pre-incubated with purified ECM proteins), adhesion of GEC to collagen I, collagen IV, laminin, and fibronectin was inhibited with anti-beta 1 integrin antibody. The peptide RGDS inhibited adhesion to fibronectin and laminin. Immunoprecipitation studies demonstrated the presence of alpha 2, alpha 3, and beta 1 integrins; the alpha 1, alpha 4, alpha 5, alpha 6, alpha v, and beta 3 subunits were undetectable. Adhesion to all ECM proteins was dependent on divalent cations, but the effects of individual cations varied among substrata. In rat GEC, alpha 2 beta 1 and/or alpha 3 beta 1 integrins appear to mediate adhesion to collagen I, collagen IV, and laminin. The alpha 3 beta 1 integrin is also the likely receptor for fibronectin, interacting through an RGD binding site. Furthermore, single integrins or combinations of integrins appear to have distinct ligand-binding functions that are differentially regulated by divalent cations. Characterization of GEC adhesion molecules may facilitate the understanding of mechanisms of glomerular development, and cell detachment or proliferation in immune glomerular injury.

Cyclic stretch-induced TGF-β1 and fibronectin expression is mediated by β1-integrin through c-Src- and STAT3-dependent pathways in renal epithelial cells

“…In Alport mice, the expression of ␣v␤6 correlates with renal fibrosis, and blocking this integrin results in reduced deposition of collagen matrix (21). In several models of kidney diseases, ablation of ␤1-integrin abrogates profibrotic signaling and blocks accumulation of ECM and the development of tubulointerstitial fibrosis (15,36,70). However, the molecular mechanisms by which ␤1-integrin attenuates UUO-induced fibrosis are not well characterized.…”

Arg-Gly-Asp (RGD) Peptides and Peptidomimetics as Therapeutics: Relevance for Renal Diseases

“…The majority of β 1 integrin dimers,including those with RGD-binding capacity, are present on some or all of the different cellular constituents of the kidney (the distribution of integrin and other cell adhesion receptors in the kidney is discussed in detail elsewhere in this issue [reviews by Wilson and Burrow, Pröls and colleagues, Mundel and Shankland, Rosenkranz and Mayadas, Norman and Fine, key references 24, 25, 26, 27, 28, 29]. In addition, certain specialized adhesion proteins are present in the kidney in a more restricted distribution; for example, lymphocyte function associated molecules (LFA) on leukocytes and endothelial cell adhesion receptors are involved in inflammatory cell migration [see the review by Rosenkranz and Mayadas]: gpIIbIIIa (α IIb β 3 ) on platelets and α v β 3 on mesangial cells.…”

Cystic Diseases of the Kidney: Role of Adhesion Molecules in Normal and Abnormal Tubulogenesis

“…The α 3 β 1 integrin has been shown to mediate adhesion to collagen types I and IV and to laminin in vitro and is probably the receptor for fibronectin [52]. It is thought to be involved in the establishment and/or maintenance of basement membrane integrity and to regulate stress fiber formation.…”