Role of mTOR signaling in the activation of renal interstitial fibroblasts
10.3760/cma.j.issn.1001-7097.2012.03.014
- VernacularTitle:mTOR通路调控肾间质成纤维细胞活化的机制
- Author:
Guochun CHEN
;
Hong LIU
;
Chang WANG
;
Xun ZHOU
;
Fuyou LIU
- Publication Type:Journal Article
- Keywords:
Fibrosis;
Fibroblasts;
Rapamycin;
mTOR signaling
- From:
Chinese Journal of Nephrology
2012;28(3):226-231
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the regulatory role of mTOR signaling in activation of renal interstitial fibroblasts and the potential effect on interstitial fibrosis. Methods 8-week old female C57BL/6 mice (n=30) underwent unilateral ureteral obstruction (UUO) to induce renal interstitial fibrosis. Animals were randomly divided into rapamycin (2 mg·kg-1· d-1) group and UUO group (vehicle-treated) (n=15 each group). Daily intraperitoneal injection of rapamycin or saline was applied to animals from day 1 before operation to the end of experiment.Three mice were sacrificed at day 1,3,7,14 respectively and kidneys were harvested for further analysis.NIH3T3 cells were stimulated by TGF-β for 12 hours with the presence or bsence of rapamycin (100 nmol/L). Results Immunofluorescent co-staining revealed that active fibroblasts highly expressed pS6K and α-SMA in kidney interstitium.Administation of rapamycin significantly inhibited activation of mTOR signaling in fibroblasts and ameliorated interstitial fibrosis of obstructed kidneys.Real-time PCR confirmed that rapamycin decreased the mRNA expression of FSP1,TGF-β,CTGF and Col4A1 in fibrotic kidneys. In vitro experiment revealed that TGF-β induced highly expression of pS6K and αSMA in cultured NIH3T3 cells,which could be markedly inhibited by rapamycin. Conclusions mTOR signaling highly activates in interstitial fibroblasts during kidney fibrosis.Inhibition of mTOR signaling by rapamycin decreases the activation of fibroblasts and ameliorates interstitial fibrosis.
