Inhibition of integrin α2β1 ameliorates glomerular injury.

Borza CM, Su Y, Chen X, Yu L, Mont S, Chetyrkin S, Voziyan P, Hudson BG, Billings PC, Jo H, Bennett JS, Degrado WF, Eckes B, Zent R, Pozzi A
J Am Soc Nephrol. 2012 23 (6): 1027-38

PMID: 22440900 · PMCID: PMC3358756 · DOI:10.1681/ASN.2011040367

Mesangial cells and podocytes express integrins α1β1 and α2β1, which are the two major collagen receptors that regulate multiple cellular functions, including extracellular matrix homeostasis. Integrin α1β1 protects from glomerular injury by negatively regulating collagen production, but the role of integrin α2β1 in renal injury is unclear. Here, we subjected wild-type and integrin α2-null mice to injury with adriamycin or partial renal ablation. In both of these models, integrin α2-null mice developed significantly less proteinuria and glomerulosclerosis. In addition, selective pharmacological inhibition of integrin α2β1 significantly reduced adriamycin-induced proteinuria, glomerular injury, and collagen deposition in wild-type mice. This inhibitor significantly reduced collagen synthesis in wild-type, but not integrin α2-null, mesangial cells in vitro, demonstrating that its effects are integrin α2β1-dependent. Taken together, these results indicate that integrin α2β1 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.

MeSH Terms (20)

Acute Kidney Injury Albuminuria Analysis of Variance Animals Blotting, Western Disease Models, Animal Doxorubicin Enzyme-Linked Immunosorbent Assay Flow Cytometry Immunohistochemistry Integrin alpha2beta1 Kidney Function Tests Kidney Glomerulus Male Mesangial Cells Mice Mice, Inbred BALB C Mice, Knockout Random Allocation Receptors, Collagen

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