Lack of 8-integrin aggravates podocyte injury in experimental diabetic nephropathy

نویسندگان

  • Andrea Hartner
  • Nada Cordasic
  • Carlos Menendez-Castro
  • Gudrun Volkert
  • Julie M. Yabu
  • Miroslava Kupraszewicz-Hutzler
  • Wolfgang Rascher
  • Karl F. Hilgers
چکیده

Hartner A, Cordasic N, Menendez-Castro C, Volkert G, Yabu JM, Kupraszewicz-Hutzler M, Rascher W, Hilgers KF. Lack of 8integrin 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 8-integrin chain is specifically expressed in mesangial cells of the glomerulus. During experimental hypertension, 8-integrin plays a protective role in the glomerulus. We hypothesized that 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 8-integrin. To test the functional role of 8-integrin, STZ diabetes was induced in mice with a homozygous ( 8 / ) or heterozygous ( 8 / ) deletion of the 8-integrin gene and in wild-type litters ( 8 / ). Blood glucose and mean arterial blood pressure were not different in 8 / and 8 / mice after 6 wk of diabetes. However, diabetic 8 / mice developed significantly higher albuminuria and more glomerulosclerosis than diabetic 8 / mice. Moreover, in diabetic 8 / mice, the number of glomerular cells staining positive for the podocyte markers WT-1 and vimentin were reduced more prominently than in diabetic 8 / . The filtration barrier protein nephrin was downregulated in diabetic glomeruli with the strongest reduction observed in 8 / mice. Taken together, 8 / mice developed more severe glomerular lesions and podocyte damage after onset of STZ diabetes than 8 / mice, indicating that 8-integrin is protective for the structure and function of the glomerulus and maintains podocyte integrity during the development of diabetic nephropathy.

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تاریخ انتشار 2010