Julie M. Yabu

Publication Details

  • Lack of alpha 8-integrin aggravates podocyte injury in experimental diabetic nephropathy AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY Hartner, A., Cordasic, N., Menendez-Castro, C., Volkert, G., Yabu, J. M., Kupraszewicz-Hutzler, M., Rascher, W., Hilgers, K. F. 2010; 299 (5): F1151-F1157


    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.

    View details for DOI 10.1152/ajprenal.00058.2010

    View details for Web of Science ID 000283846800027

    View details for PubMedID 20826576

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