Department of Pediatrics, The First Affiliated Hospital of GuangXi Medical University, NanNing 530021, China.
Ren Fail. 2013;35(2):262-7. doi: 10.3109/0886022X.2012.745120. Epub 2012 Nov 26.
All-trans retinoic acid (ATRA) is an important therapeutic agent for prevention of the renal diseases. Transforming growth factor-β1 (TGF-β1)/Smad3 signaling pathway is a key signaling pathway which takes part in the progression of renal interstitial fibrosis (RIF). This investigation was performed to study the effect of ATRA in RIF rats and its effect on the TGF-β1/Smad3 signaling pathway. Sixty Wistar male rats were divided into three groups at random: sham operation group (SHO), model group subjected to unilateral ureteral obstruction (GU), model group treated with ATRA (GA), n = 20, respectively. RIF index, protein expression of TGF-β1, collagen-IV (Col-IV) and fibronectin (FN) in renal interstitium, and mRNA and protein expressions of Smad3 in renal tissue were detected at 14-day and 28-day after surgery. The RIF index was markedly elevated in group GU than in SHO group (p < 0.01), and the RIF index of GA group was alleviated when compared with that in GU group (p < 0.01). Compared with in group SHO, the mRNA/protein expression of Smad3 in renal tissue was significantly increased in group GU (p < 0.01). However, the mRNA and protein expressions of Smad3 in renal tissue in GA group were not markedly alleviated by ATRA treatment when compared with those in GU (each p > 0.05). Protein expressions of TGF-β1, Col-IV, and FN in GU group were markedly increased than those in SHO group (each p < 0.01), and their expressions in GA group were markedly down-regulated by ATRA treatment than those of GU group (all p < 0.01). The protein expression of Smad3 was positively correlated with RIF index, protein expression of TGF-β1, Col-IV or FN (each p < 0.01). In conclusion, ATRA treatment can alleviate the RIF progression in UUO rats. However, ATRA cannot affect the signaling pathway of TGF-β1/Smad3 in the progression of RIF.
全反式视黄酸(ATRA)是预防肾脏疾病的重要治疗药物。转化生长因子-β1(TGF-β1)/Smad3 信号通路是参与肾间质纤维化(RIF)进展的关键信号通路。本研究旨在探讨 ATRA 对单侧输尿管梗阻(UUO)大鼠 RIF 的作用及其对 TGF-β1/Smad3 信号通路的影响。60 只 Wistar 雄性大鼠随机分为三组:假手术组(SHO)、单侧输尿管梗阻模型组(GU)、ATRA 治疗组(GA),每组 20 只。术后 14 天和 28 天检测肾间质 TGF-β1、胶原-IV(Col-IV)和纤维连接蛋白(FN)蛋白表达及肾组织 Smad3mRNA 和蛋白表达,计算肾间质纤维化指数(RIF 指数)。与 SHO 组比较,GU 组 RIF 指数明显升高(p<0.01),GA 组 RIF 指数低于 GU 组(p<0.01)。与 SHO 组比较,GU 组肾组织 Smad3mRNA/蛋白表达明显升高(p<0.01);与 GU 组比较,GA 组 Smad3mRNA 和蛋白表达虽有降低,但差异无统计学意义(p>0.05)。GU 组 TGF-β1、Col-IV 和 FN 蛋白表达明显高于 SHO 组(p<0.01),GA 组 TGF-β1、Col-IV 和 FN 蛋白表达明显低于 GU 组(p<0.01)。Smad3 蛋白表达与 RIF 指数及 TGF-β1、Col-IV 或 FN 蛋白表达呈正相关(p<0.01)。结论:ATRA 治疗可减轻 UUO 大鼠 RIF 的进展,但不能影响 TGF-β1/Smad3 信号通路在 RIF 进展中的作用。