Lack of α8-integrin aggravates podocyte injury in experimental diabetic nephropathy

Hartner A, Cordasic N, Menendez-Castro C, Volkert G, Yabu JM, Kupraszewicz-Hutzler M, Rascher W, Hilgers KF. Lack of alpha 8-integrin aggravates podocyte injury in experimental diabetic nephropathy. Am J Physiol Renal Physiol 299: F1151-F1157, 2010. First published September 8, 2010; doi:10.1152/ajprenal.00058.2010.-Development of diabetic nephropathy is accompanied by changes in integrin-mediated cell-matrix interactions. The alpha 8-integrin chain is specifically expressed in mesangial cells of the glomerulus. During experimental hypertension, alpha 8-integrin plays a protective role in the glomerulus. We hypothesized that alpha 8-integrin is involved in maintaining the integrity of the glomerulus in diabetic nephropathy. Experimental streptozotocin (STZ) diabetes led to an increased expression and glomerular deposition of alpha 8-integrin. To test the functional role of alpha 8-integrin, STZ diabetes was induced in mice with a homozygous (alpha 8-/-) or heterozygous (alpha 8+/-) deletion of the alpha 8-integrin gene and in wild-type litters (alpha 8+/+). Blood glucose and mean arterial blood pressure were not different in alpha 8-/- and alpha 8+/+ mice after 6 wk of diabetes. However, diabetic alpha 8-/- mice developed significantly higher albuminuria and more glomerulosclerosis than diabetic alpha 8+/+ mice. Moreover, in diabetic alpha 8-/- mice, the number of glomerular cells staining positive for the podocyte markers WT-1 and vimentin were reduced more prominently than in diabetic alpha 8+/+. The filtration barrier protein nephrin was downregulated in diabetic glomeruli with the strongest reduction observed in alpha 8-/- mice. Taken together, alpha 8-/- mice developed more severe glomerular lesions and podocyte damage after onset of STZ diabetes than alpha 8+/+ mice, indicating that alpha 8-integrin is protective for the structure and function of the glomerulus and maintains podocyte integrity during the development of diabetic nephropathy.