Sorafenib ameliorates renal fibrosis through inhibition of TGF-β/Smad pathway
10.7652/jdyxb201603016
- VernacularTitle:Sorafenib通过抑制TGF-β/Smad途径延缓肾纤维化的研究
- Author:
Lining JIA
;
Xiaotao MA
;
Yang YANG
;
Rongguo FU
;
Baosong GUI
- Publication Type:Journal Article
- Keywords:
sorafenib;
renal fibrosis;
epithelial-mesenchymal transition (EMT);
transforming growth factor-β(TGF-β);
Smad3
- From:
Journal of Xi'an Jiaotong University(Medical Sciences)
2016;37(3):378-382,398
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of sorafenib in ameliorating renal fibrosis and its possible mechanisms.Methods Rats were subjected to unilateral ureteral obstruction (UUO ) and intragastrically administered sorafenib.NRK-52E cells were treated with transforming growth factor-β1 (TGF-β1)and sorafenib. HE staining was used to visualize renal fibrosis.α-SMA and E-cadherin expressions in kidney tissue and NRK-52E cells were performed using immunofluorescence.The cell cycle of NRK-52E cells was determined by flow cytometry analysis.Smad3 and p-Smad3 protein expressions in NRK-52E cells were detected by Western blot analysis. Results HE staining showed that kidney interstitial fibrosis,tubular atrophy,and inflammatory cell infiltration in the sorafenib-treated UUO groups were significantly decreased compared with the vehicle-treated UUO group (P<0.05).Compared with those in UUO and TGF-β-stimulated NRK-52E groups,the expression of a-SMA decreased but E-cadherin expression increased in the UUO kidneys and NRK-52E cells of the sorafenib-treated groups (P<0.05).After 24 h stimulation with TGF-β1 5 ng/mL,the number of cell cycles arrested in G0/G1 phase was significantly increased and the number of cells that entered G2 ,S phase decreased (P<0 .0 5 ).Compared with that in TGF-β-stimulated NRK-52E groups, p-Smad3 decreased in the sorafenib-treated groups (P<0.05). Conclusion Our results suggest that sorafenib may be useful for the treatment of renal fibrosis through suppressing TGF-β/Smad3 signaling.
