Selective binding of integrins from different renal cell types to the NC1 domain of α3 and α1 chains of type IV collagen

Background: Cells interact with type IV collagen (Col IV) via integrins through the triple-helical and NC1 domains. We examined interactions of human glomerular and proximal tubular epithelial cells with recombinant a1 and a3 NC1 chains of Col IV, to explore the ability of different cell types to interact with Col IV of different trimer composition. Methods: Interactions of TSV-40-immortalized human glomerular epithelial cells (HGECs), HPV-16-immortalized human proximal tubular epithelial (HK-2) cells and primary human mesangial cells (MES) with recombinant α1 and α3 NC1 chains of Col IV were examined by affinity chromatography and solid-phase binding assays. The expression of integrin-regulated metalloproteinases was examined by zymography. Results: HGECs bound to both α3 and α1(IV)NC1, albeit there was preferential binding to α3(IV)NC1, through the α3β1 and α2β1 integrin receptors; HK-2 cells and MES bound almost exclusively to a1(IV)NC1 via the α3β1/αvβ3 and α1β1/α2β1 receptors, respectively. It was demonstrated that the expression of MMP-2 and MMP-9 by HGECs was down-regulated in the presence of α3(IV)NC1. Conclusions: The observed data indicate that the isoform NC1 chains of Col IV serve for selective, integrin-mediated cell binding which probably triggers different signaling mechanisms, resulting in the activation of specific transcription factors and the modulation of gene expression.