| First Author | Hartner A | Year | 2010 |
| Journal | Am J Physiol Renal Physiol | Volume | 299 |
| Issue | 5 | Pages | F1151-7 |
| PubMed ID | 20826576 | Mgi Jnum | J:165581 |
| Mgi Id | MGI:4837782 | Doi | 10.1152/ajprenal.00058.2010 |
| Citation | Hartner A, et al. (2010) Lack of {alpha}8-integrin aggravates podocyte injury in experimental diabetic nephropathy. Am J Physiol Renal Physiol 299(5):F1151-7 |
| abstractText | Development of diabetic nephropathy is accompanied by changes in integrin-mediated cell-matrix interactions. The alpha8-integrin chain is specifically expressed in mesangial cells of the glomerulus. During experimental hypertension, alpha8-integrin plays a protective role in the glomerulus. We hypothesized that alpha8-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 alpha8-integrin. To test the functional role of alpha8-integrin, STZ diabetes was induced in mice with a homozygous (alpha8-/-) or heterozygous (alpha8+/-) deletion of the alpha8-integrin gene and in wild-type litters (alpha8+/+). Blood glucose and mean arterial blood pressure were not different in alpha8-/- and alpha8+/+ mice after 6 wk of diabetes. However, diabetic alpha8-/- mice developed significantly higher albuminuria and more glomerulosclerosis than diabetic alpha8+/+ mice. Moreover, in diabetic alpha8-/- mice, the number of glomerular cells staining positive for the podocyte markers WT-1 and vimentin were reduced more prominently than in diabetic alpha8+/+. The filtration barrier protein nephrin was downregulated in diabetic glomeruli with the strongest reduction observed in alpha8-/- mice. Taken together, alpha8-/- mice developed more severe glomerular lesions and podocyte damage after onset of STZ diabetes than alpha8+/+ mice, indicating that alpha8-integrin is protective for the structure and function of the glomerulus and maintains podocyte integrity during the development of diabetic nephropathy. |
