| First Author | Ishigaki N | Year | 2007 |
| Journal | Biochem Biophys Res Commun | Volume | 364 |
| Issue | 3 | Pages | 502-8 |
| PubMed ID | 17961514 | Mgi Jnum | J:128446 |
| Mgi Id | MGI:3767124 | Doi | 10.1016/j.bbrc.2007.10.038 |
| Citation | Ishigaki N, et al. (2007) Involvement of glomerular SREBP-1c in diabetic nephropathy. Biochem Biophys Res Commun 364(3):502-8 |
| abstractText | The role of glomerular SREBP-1c in diabetic nephropathy was investigated. PEPCK-promoter transgenic mice overexpressing nuclear SREBP-1c exhibited enhancement of proteinuria with mesangial proliferation and matrix accumulation, mimicking diabetic nephropathy, despite the absence of hyperglycemia or hyperlipidemia. Isolated transgenic glomeruli had higher expression of TGFbeta-1, fibronectin, and SPARC in the absence of marked lipid accumulation. Gene expression of P47phox, p67phox, and PU.1 were also activated, accompanying increased 8-OHdG in urine and kidney, demonstrating that glomerular SREBP-1c could directly cause oxidative stress through induced NADPH oxidase. Similar changes were observed in STZ-treated diabetic mice with activation of endogenous SREBP-1c. Finally, diabetic proteinuria and oxidative stress were ameliorated in SREBP-1-null mice. Adenoviral overexpression of active and dominant-negative SREBP-1c caused consistent reciprocal changes in expression of both profibrotic and oxidative stress genes in MES13 mesangial cells. These data suggest that activation of glomerular SREBP-1c could contribute to emergence and/or progression of diabetic nephropathy. |
