Abstract
Expression of integrin, which mediates cell–matrix interaction, is affected by several cytokines, in particular by transforming growth factor-β (TGF-β). However, it is unknown whether, in an opposite way, a specific integrin is involved in cytokine synthesis. We tested this hypothesis. Function-blocking anti-α5 integrin (fibronectin receptor) antibody increased TGF-β secretion in growth-arrested human mesangial cells (2.3-fold) compared with control IgG or anti-αvβ3 integrin (receptor for several matrix proteins) antibody. It also increased the secretion of plasminogen activator inhibitor-1 (PAI-1), a protein associated with matrix increase, by 3.2-fold. The increase in PAI-1 secretion induced by anti-α5 integrin antibody was not abrogated by anti-TGF-β neutralizing antibody. These results indicate that function-blocking of anti-α5 integrin stimulates TGF-β as well as PAI-1 production, suggesting that α5 integrin is involved in fibrotic process. Function-modulation of a specific integrin thus appears to play a role in glomerular remodeling.
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