Expressions and Effects of Transforming Growth Factor-β1Smad3 Signaling Pathway in Renal Tubulointerstital Fibrosis Rats

Objective To explore the expressions of transforming growth factor-β1(TGF-β1)and Smad3 after unilateral ureteral obstruction(UUO) in rats and to investigate the effects and mechanisms of TGF-β1/Smad3 signaling pathway in renal tubulointerstitial fibrosis(RIF). Methods Forty-eight Wistar male rats(6-week-old) were randomly assigned into sham operation group(n=24) and UUO group(n=24).The left ureter of rats in UUO group were dissociated to be obstructed after anesthesia.The rats in sham operation group were dissociated left ureter only,and not to be obstructed.Six rats in the 2 groups were killed respectively at the 7~th,14~th,21~th,28~th days after surgery,the left kidney were collected.Histological changes of renal tubular interstitium were observed by HE and Masson staining,and the index of RIF was calculated.Western blot and real-time fluorescent quantitative polymerase chain reaction(PCR) were performed to detect the protein and mRNA expression of Smad3.The expression of protein of TGF-β1,collagen-Ⅳ(Col-Ⅳ),fibronectin(FN) were detected by immunohistochemistry method. Results 1.Compared to the sham operation group,at each same point of time of UUO group:(1)Pathologic study showed that renal tubular epithelial cell atrophy,collagen fibrosis and diffuse mononucler cells,lymphocyte infiltration in UUO group.The index of RIF in UUO group was increased remarkably(P0.01),the longer the obstruction,the higher the RIF index;(2)The expressions of protein and mRNA of Smad3 in UUO group were all significantly increased,the longer the obstruction,the higher the expression level;(3)The expressions of protein of TGF-β1,Col-Ⅳ,FN in UUO group were all significantly increased(P_a0.05),the longer the obstruction,the higher the expression level.2.Correlation analysis showed that:(1)the expressions of protein of Smad3 and TGF-β1 in UUO group were positive correlations with the index of RIF(r=0.520,0.727,P_a 0.01);(2)the expressions of protein of Col-Ⅳand FN were positive correlations with the index of RIF(r= 0.794,0.786,P_a0.01);(3)the expression of protein of Smad3 were positive correlation with all the expresssions of TGF-β1,Col-Ⅳ,FN(r= 0.592,0.672,0.508,P_a0.01). Conclusions The expressions of TGF-β1 and Smad3 were all increased in renal tissues of UUO rats,the longer the obstruction,the higher the expression level,the more severe the RIF degree.TGF-β1/Smad3 signaling pathway may be involved in the development of RIF.