| First Author | Menne J | Year | 2004 |
| Journal | Diabetes | Volume | 53 |
| Issue | 8 | Pages | 2101-9 |
| PubMed ID | 15277392 | Mgi Jnum | J:107195 |
| Mgi Id | MGI:3620397 | Doi | 10.2337/diabetes.53.8.2101 |
| Citation | Menne J, et al. (2004) Diminished loss of proteoglycans and lack of albuminuria in protein kinase C-alpha-deficient diabetic mice. Diabetes 53(8):2101-9 |
| abstractText | Activation of protein kinase C (PKC) isoforms has been implicated in the pathogenesis of diabetic nephropathy. We showed earlier that PKC-alpha is activated in the kidneys of hyperglycemic animals. We now used PKC-alpha(-/-) mice to test the hypothesis that this PKC isoform mediates streptozotocin-induced diabetic nephropathy. We observed that renal and glomerular hypertrophy was similar in diabetic wild-type and PKC-alpha(-/-) mice. However, the development of albuminuria was almost absent in the diabetic PKC-alpha(-/-) mice. The hyperglycemia-induced downregulation of the negatively charged basement membrane heparan sulfate proteoglycan perlecan was completely prevented in the PKC-alpha(-/-) mice, compared with controls. We then asked whether transforming growth factor-beta1 (TGF-beta1) and/or vascular endothelial growth factor (VEGF) is implicated in the PKC-alpha-mediated changes in the basement membrane. The hyperglycemia-induced expression of VEGF165 and its receptor VEGF receptor II (flk-1) was ameliorated in PKC-alpha(-/-) mice, whereas expression of TGF-beta1 was not affected by the lack of PKC-alpha. Our findings indicate that two important features of diabetic nephropathy-glomerular hypertrophy and albuminuria-are differentially regulated. The glucose-induced albuminuria seems to be mediated by PKC-alpha via downregulation of proteoglycans in the basement membrane and regulation of VEGF expression. Therefore, PKC-alpha is a possible therapeutic target for the prevention of diabetic albuminuria. |
