Influence of SOCS-1 on AGEs-induced renal tubular epithelial-myofibroblast transdifferentiation
- VernacularTitle:细胞因子信号传导抑制蛋白1对糖基化终末产物诱导的肾小管细胞转分化的影响
- Author:
Yonghong SHI
;
Yunzhuo REN
;
Song ZHAO
;
Jun HAO
;
Fang YAO
;
Wei LIU
;
Haijiang WU
;
Huijun DUAN
- Publication Type:Journal Article
- Keywords:
suppressor of cytokine signaling-1;
advanced glycation end products;
signal transducer and activatior of transcription 1;
signal transducer and activatior of transcription 3;
tubular epithelial cells;
transdifferentiation
- From:
Chinese Pharmacological Bulletin
2010;26(2):190-194
- CountryChina
- Language:Chinese
-
Abstract:
Aim To investigate the effects of suppressor of cytokine signaling-1(SOCS-1)on advanced glycation end products(AGEs)induced-renal tubular epithelial-myofibroblast transdifferentiation and activation of JAK/STAT in cultured human renal tubular epithelial cells(HKC).Methods Stable transfections of HKC with pCR3.1 vector and pCR3.1/SOCS-1 were performed with Lipofectamine 2000,and cells were selected with geneticin.Cells were stimulated with BSA and AGEs. The protein expressions of SOCS-1,α-SMA,E-cadherin,Col I,signal transducer and activatior of transcription 1,3(STAT1,STAT3),p-STAT1 and p-STAT3 were observed by Western blot.The protein synthesis of TGF-β_1 in the supernatants of the HKC was detected by enzyme-linked immunoadsorbent assay(ELISA).α-SMA and E-cadherin mRNA were measured by reverse transcription and polymerase chain reaction(RT-PCR).Results Compared with control group,the expression levels of α-SMA protein and mRNA and Col I were significantly increased in HKC with AGEs stimulation and there was a higher concentrations of TGF-β_1 in the supernatants.However,the expression of E-cadherin protein and mRNA were decreased with AGEs stimulation.Overexpression of SOCS-1 inhibited AGEs-induced activation of STAT1 and STAT3 and high expression of α-SMA protein and mRNA and Col I,and reversed the expression of E-cadherin protein and mRNA induced by AGEs.Meanwhile,overexpression of SOCS-1 reduced the concentration of TGF-β_1 in the supernatants of HKC with AGEs stimulation.Conclusion Overexpression of SOCS-1 inhibits AGEs-induced renal tubular epithelial-myofibroblast transdifferentiation maybe partly through blocking activation of JAK/STAT.