Adriamycin nephropathy > Background Section
Adriamycin administration induces a progressive nephropathy in rats, but most mice strains are resistant (). However, Balb/c mice will develop moderate glomerular injury over a 2-6 week time course. Balb/c mice with selective deletion of integrin α1, a single dose of adriamycin (10 mg/kg) induces significantly more glomerulosclerosis, accompanied by increased glomerular collagen production mesangiolysis and foot process effacement compared to wild type Balb/c (8).
Publications for Adriamycin nephropathy (1)
Chen X, Moeckel G, Morrow JD, Cosgrove D, Harris RC, Fogo AB, Zent R, Pozzi A. Lack of integrin alpha1beta1 leads to severe glomerulosclerosis after glomerular
injury. Am J Pathol (2004) 165:617-30
View abstract View in PubMed
Severity of fibrosis after injury is determined by the nature of the injury and host genetic susceptibility. Metabolism of collagen, the major component of fibrotic lesions, is, in part, regulated by integrins. Using a model of glomerular injury by adriamycin, which induces reactive oxygen species (ROS) production, we demonstrated that integrin alpha1-null mice develop more severe glomerulosclerosis than wild-type mice. Moreover, primary alpha1-null mesangial cells produce more ROS both at baseline and after adriamycin treatment. Increased ROS synthesis leads to decreased cell proliferation and increased glomerular collagen IV accumulation that is reversed by antioxidants both in vivo and in vitro. Thus, we have identified integrin alpha1beta1 as a modulator of glomerulosclerosis. In addition, we showed a novel pathway where integrin alpha1beta1 modulates ROS production, which in turn controls collagen turnover and ultimately fibrosis. Because integrin alpha1beta1 is expressed in many cell types this may represent a generalized mechanism of controlling matrix accumulation, which has implications for numerous diseases characterized by fibrosis.
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Last updated on 2013-11-06 Moderated by Raymond Harris