Inhibition of Integrin α2β1 Ameliorates Glomerular Injury

Mesangial cells and podocytes express integrins alpha 1 beta 1 and alpha 2 beta 1, which are the two major collagen receptors that regulate multiple cellular functions, including extracellular matrix homeostasis. Integrin alpha 1 beta 1 protects from glomerular injury by negatively regulating collagen production, but the role of integrin alpha 2 beta 1 in renal injury is unclear. Here, we subjected wild-type and integrin alpha 2-null mice to injury with adriamycin or partial renal ablation. In both of these models, integrin alpha 2-null mice developed significantly less proteinuria and glomerulosclerosis. In addition, selective pharmacological inhibition of integrin alpha 2 beta 1 significantly reduced adriamycin-induced proteinuria, glomerular injury, and collagen deposition in wildtype mice. This inhibitor significantly reduced collagen synthesis in wild-type, but not integrin alpha 2-null, mesangial cells in vitro, demonstrating that its effects are integrin alpha 2 beta 1-dependent. Taken together, these results indicate that integrin alpha 2 beta 1 contributes to glomerular injury by positively regulating collagen synthesis and suggest that its inhibition may be a promising strategy to reduce glomerular injury and proteinuria.