Back to Search
Start Over
TGF-beta1 reduces Wilms' tumor suppressor gene expression in podocytes.
- Source :
-
Nephrology Dialysis Transplantation . Sep2011, Vol. 26 Issue 9, p2746-2752. 7p. - Publication Year :
- 2011
-
Abstract
- Background. Wilms' tumor suppressor gene (WT1) is essential for normal podocyte function, and transforming growth factor (TGF)-beta contributes to focal segmental glomerulosclerosis (FSGS). We aimed to address whether TGF-beta affects WT1 expression in podocytes.Methods. A human podocyte cell line treated with TGF-beta1 and kidneys in Alb/TGF-beta1-transgenic mice were analyzed for WT1 expression.Results. In cultured podocytes, TGF-beta1 reduced WT1 protein expression determined by western blotting beginning at 8 h and decreased WT1 messenger RNA (mRNA) expression measured by quantitative reverse transcription–polymerase chain reaction beginning at 3 h. Knockdown of Smad4 by small hairpin (sh) RNA partially rescued the TGF-beta1-induced reduction of both WT1 protein and mRNA expressions in the cultured podocytes. TGF-beta1 did not alter luciferase activity of the reporter construct for a human WT1 promoter but reduced that for a human WT1 5′ enhancer construct, suggesting that TGF-beta1 may regulate WT1 expression by altering the 5′ enhancer activity. In the transgenic mice, WT1 protein expression in podocytes was decreased at 1 and 3 weeks of age, while glomeruloclerosis developed after 3 weeks.Conclusion. TGF-beta1 reduces WT1 expression in cultured human podocytes and podocytes in mice before overt glomerulosclerosis begins. The effects are at least partially Smad4 dependent. Our findings identify a novel pathway linking TGF-beta1 to podocyte injury and FSGS. The WT1 reduction may be a useful marker for early podocyte injury. [ABSTRACT FROM PUBLISHER]
Details
- Language :
- English
- ISSN :
- 09310509
- Volume :
- 26
- Issue :
- 9
- Database :
- Academic Search Index
- Journal :
- Nephrology Dialysis Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 65581693
- Full Text :
- https://doi.org/10.1093/ndt/gfr061