| First Author | Cheng J | Year | 2010 |
| Journal | Kidney Int | Volume | 78 |
| Issue | 7 | Pages | 668-78 |
| PubMed ID | 20631674 | Mgi Jnum | J:184255 |
| Mgi Id | MGI:5320552 | Doi | 10.1038/ki.2010.214 |
| Citation | Cheng J, et al. (2010) Serum- and glucocorticoid-regulated kinase 1 is upregulated following unilateral ureteral obstruction causing epithelial-mesenchymal transition. Kidney Int 78(7):668-78 |
| abstractText | Obstructive nephropathy leads to chronic kidney disease, characterized by a progressive epithelial-to-mesenchymal cell transition (EMT)-driven interstitial fibrosis. To identify the mechanisms causing EMT, we used the mouse model of unilateral ureteral obstruction and found a rapid and significant increase in serum- and glucocorticoid-regulated kinase-1 (SGK1) expression in the kidneys with an obstructed ureter. Knockout of SGK1 significantly suppressed obstruction-induced EMT, kidney fibrosis, increased glycogen synthase kinase-3beta activity, and decreased accumulation of the transcriptional repressor Snail. This caused a reduced expression of the mesenchymal marker alpha-smooth muscle actin, and collagen deposition in this model. In cultured kidney epithelial cells, mechanical stretch or treatment with transforming growth factor-beta not only stimulated the transcription of SGK1, but also stimulated EMT in an SGK1-dependent manner. Activated SGK1 stimulated Snail accumulation and downregulation of the epithelial marker E-cadherin. Hence, our study shows that SGK1 is involved in mediating fibrosis associated with obstructive nephropathy. |
