| OBJECTIVE To explore the expression of transforming growth factor-β1(TGF-β1) and Smad3 in renal tubulointerstitial fibrosis (RIF) of rats after unilateral ureteral obstruction (UUO) and investigate the effects of TGF-β1/Smad3 signaling pathway in RIF.METHOD Forty-eight Wistar male rats (6-week-old) were randomly assigned into sham operation group and UUO group. 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 of the two groups were killed respectively at 7, 14, 21, 28 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. The expression of protein of TGF-β1,collagen-Ⅳ(Col-Ⅳ), fibronectin (FN) were detected by Immunohistochemistry method. Western blot andreal-time fluorescent quantitative polymerase chain reaction (RT-PCR) were respectively performed to detect the protein and mRNA expression of Smad3.RESULT 1.Compared to the sham operation group, at each same pointof time, (1) Pathologic study showed that, renal tubular epithelial cell atrophy collagen fibrosis and diffuse mononuclear cells, lymphocyte infiltration in UUO, group. The index of RIF in UUO group was increased remarkably (P<0. 01), the longer the obstruction, the higher the RIF index; (2) The expression of protein and mRNA of Smad3 in UUO group were all significantly increased, the longer the obstruction, the higher the expression level; (3) The expression of protein of TGF-β1, Col-Ⅳ, FN in UUO group were all significantly increased, the longer the obstruction, the higher the expression level. 2. Correlation analysis showed that: the expression of protein of Smad3 and TGF-β1 in UUO group was positive correlation with the index of RIF( r = 0.520, 0.727, P< 0. 01), the expression of protein of Col-Ⅳand FN were positive correlations with the index of RIF(r= 0.794, 0.786, P<0.01), and the expression of protein of Smad3 was positive correlation with all the expresssion of TGF-β1, Col-Ⅳ, FN(r= 0.592,0.672, 0.508, P<0.01).CONCLUSIONS The expression 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 involved in The development of RIF. OBJECTIVE To observe the effects of ATRA on the expression of TGF-β1 and Smad3 in the renal tissue of rats with RIF and to investigate the mechanisms of ATRA to TGF-β1/Smad3 signaling pathway in RIF.METHOD Seventy-two Wistar male rats (6-week-old) were randomly assigned into three groups: sham operation group, UUO group and ATRA group. Six rats of the three groups were killed respectively at 7, 14, 21, 28 days after surgery. Histological changes of renal tubular interstitium were observed by HE and Masson staining, and the index of RIF was calculated. The expression of protein of TGF-β1, Col-Ⅳ, FN were detected by Immunohistochemistry method. Western blot and real-time RT-PCR were respectively performed to detect the protein and mRNA expression of Smad3.RESULT Compared to the UUO group, at the same point of time, the index of RIF, the expression of protein of TGF-β1, Col-Ⅳ, FN in ATRA group were all significantly decreased; but the expression of protein and mRNA of Smad3 in ATRA group were all not significantly decreased.CONCLUSIONS ATRA may delay the progress of RIF by reduce the expression of protein of TGF-β1, FN, Col-Ⅳ, but may didn't by decreasing the expression of protein and mRNA of Smad3 in TGF-β1/Smad3 signaling pathway.
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