Intercellular adhesion molecule-1 plays a critical role in glomerulosclerosis after subtotal nephrectomy

Background: Hyperfiltration in the glomeruli have been considered to be an important cause of glomerular injury; however, the role of intercellular adhesion molecule (ICAM)-1 in the pathogenesis of glomerulosclerosis is not known. Methods: To elucidate the effects of ICAM-1 depletion on hyperfiltration-induced glomerular disorder, we used subtotally nephrectomized ICAM-1^+/+ and ICAM-1^-/- mice. We evaluated macrophage infiltration, mesangial matrix expansion, transforming growth factor (TGF)-β and type IV collagen accumulation in glomeruli. Results: Macrophage infiltration into the glomeruli and mesangial matrix expansion coincident with increased expression of both ICAM-1 and TGF-β, and accumulation of type IV collagen were ameliorated in subtotally nephrectomized ICAM-1^-/- mice compared to ICAM-1^+/+ mice. ICAM-1 depletion significantly reduced hyperfiltration-induced glomerular injury after renal ablation. Conclusions: Our present findings suggest that glomerular hyperfiltration is the leading cause of glomerulosclerosis, and it is mediated, at least in part, by ICAM-1 expression and macrophage infiltration.