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Thymosin β4 alleviates renal fibrosis and tubular cell apoptosis through TGF-β pathway inhibition in UUO rat models

机译:胸腺素β4通过抑制UUO大鼠模型中的TGF-β途径减轻肾脏纤维化和肾小管细胞凋亡

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Thymosin β4 (Tβ4) is closely associated with the cytoskeleton, inflammation, wound healing, angiogenesis, apoptosis, and myocardial regeneration, but the effects of Tβ4 treatment on chronic renal tubular interstitial fibrosis (CRTIF) are poorly known. This study aimed to examine the effects of Tβ4 on the renal apoptosis and the expression of transforming growth factor (TGF-β), E-cadherin, and α-smooth muscle actin (α-SMA) in CRTIF rat models. Male SD rats were randomized into four groups (sham group, unilateral ureteral obstruction (UUO) group, UUO?+?low-dose Tβ4 group, and UUO?+?high-dose Tβ4 group). The pathological changes of kidney tissue and its function were assessed two weeks after UUO. In renal interstitial tissue,TGF-β, E-cadherin and α-SMA expression was detected by western blot. In tubular epithelial cells, E-cadherin and α-SMA expression was detected using Real-time qPCR and western blot. Cell apoptosis of rat renal interstitial tissue and tubular epithelial cells was evaluated by immunofluorescence and western blot. Two weeks after UUO, no differences in blood urea nitrogen and creatinine were observed between the four groups (P?>?0.05). Compared to the UUO group, Tβ4 treatment decreased the 24-h proteinuria (P?
机译:胸腺素β4(Tβ4)与细胞骨架,炎症,伤口愈合,血管生成,细胞凋亡和心肌再生密切相关,但是,Tβ4治疗对慢性肾小管间质纤维化(CRTIF)的影响知之甚少。这项研究旨在检查Tβ4对CRTIF大鼠模型中肾脏凋亡以及转化生长因子(TGF-β),E-钙粘着蛋白和α-平滑肌肌动蛋白(α-SMA)表达的影响。将雄性SD大鼠随机分为四组(假手术组,单侧输尿管阻塞(UUO)组,UUOβ+低剂量Tβ4组和UUOβ+β高剂量Tβ4组)。 UUO后两周评估肾脏组织的病理变化及其功能。 Western blot检测肾间质组织中TGF-β,E-cadherin和α-SMA的表达。在肾小管上皮细胞中,使用实时定量PCR和Western blot检测E-钙黏着蛋白和α-SMA的表达。用免疫荧光和蛋白质印迹法评估大鼠肾间质组织和肾小管上皮细胞的细胞凋亡。 UUO后两周,四组之间的血尿素氮和肌酐无差异(P≥0.05)。与UUO组相比,Tβ4治疗可降低24小时蛋白尿(P 0.001)并减少病理改变区域(P 0.01)。在UUO + +大剂量Tβ4组中这种作用更为明显。与UUO组相比,高剂量Tβ4组的TGF-β和α-SMA蛋白表达显着下降。 UUO组的E-钙粘蛋白水平低于Tβ4组,大剂量的Tβ4处理可进一步增加E-钙粘蛋白的表达并改善肾间质组织的细胞凋亡。体外肾小管上皮细胞的分析显示,通过Tβ4处理,α-SMAmRNA和蛋白表达降低,而E-cadherin mRNA和蛋白表达增加。同样,这些改变在UUO + +大剂量Tβ4组中更为显着。与纯TGF-β刺激相比,Tβ4处理改善了体外肾小管上皮细胞的凋亡,同样,在TGF-ββ+β大剂量Tβ4组中,凋亡的减少更为明显。 Tβ4治疗可能通过抑制CRTIF的UUO大鼠的TGF-β途径而减轻肾纤维化和肾小管上皮细胞凋亡。

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