摘要
目的:探讨阿霉素诱导的足细胞转分化(EMT)中β-catenin及TGF-β的变化及活性维生素D3干预作用。方法:以体外培养的小鼠足细胞系为研究对象,分6组进行实验:正常组(C组)、阿霉素组(即模型组,ADR组)、低剂量活性维生素D3组(LVD组)、高剂量活性维生素D3组(HVD组)、缬沙坦组(ARB组)、缬沙坦+高剂量活性维生素D3组(AHVD组)。各实验组干预24 h、48 h时通过RT-PCR检测β-catenin、TGF-βmRNA的表达,Western Bolt检测β-catenin蛋白的表达。结果:用药物干预24 h及48 h时,与正常对照组相比,ADR组足细胞β-catenin mRNA及蛋白表达均上调(P<0.01);与ADR组相比,四个药物干预组(ARB组、LVD组、HVD组、AHVD组)β-catenin mRNA及蛋白表达均下调(P<0.05)。24 h时与正常对照组相比,ADR组TGF-βmRNA表达上调(P<0.01);与ADR组相比,四个药物干预组TGF-βmRNA表达明显下调(P<0.01)。48 h时与正常对照组相比,ADR组TGF-βmRNA表达上调(P<0.01);与ADR组相比,HVD组与AHVD组TGF-βmRNA表达明显下调(P<0.01),而LVD组及ARB组无显著下降(P>0.05)。结论:活性维生素D3通过抑制信号转导通路中β-catenin、TGF-β的表达而抑制足细胞发生EMT。
Objective:To explore the role of β - catenin、TGF - β in adriamycin - induced epithelial - mesenchymal transi-tion(EMT)of podocytes and the effect of 1α,25 - dihydroxyvitamin D3 on it. Methods:Mouse podocytes in vitro cultured under dif-ferentiating conditions for 10 days were divided into 6 groups which were the control group(C group),the model group(ADR group), the low dose 1α,25 - dihydroxyvitamin D3 group(LVD group),the high dose 1α,25 - dihydroxyvitamin D3 group(HVD group),the valsartan group(ARB group)and the combination group(AHVD group,high dose 1α,25 - dihydroxyvitamin D3 combines with valsar-tan). Each group was continually incubated with drugs for 24 h and 48 h. The expression of β - catenin and TGF - β mRNA which were related to EMT was detected by reverse transcription polymerase chain reaction(RT - PCR). In addition,the expression of β -catenin protein was also detected by Western Blot. Results:After continually incubated with drugs for 24 h and 48 h,the expression of β - catenin mRNA and protein were increased in ADR group(P ﹤ 0. 01);then compared with ADR group,the expression of β -catenin mRNA and protein decreased(P ﹤ 0. 05)in ARB group,LVD group,HVD group and AHVD group. In our study,the expres-sion of TGF - βmRNA increased(P ﹤ 0. 01)in ADR group when compared with control group in 24 h;then compared with ADR group,the expression of TGF - β mRNA decreased significantly(P ﹤ 0. 01)in the four drug intervention groups. Moreover,it showed that the expression of TGF - β mRNA increased(P ﹤ 0. 01)in ADR group when compared with control group in 48 h;then compared with ADR group,the expression of TGF - β mRNA decreased significantly(P ﹤ 0. 01)in HVD group and AHVD group,but ARB group and LVD group had no significant decreased(P ﹥ 0. 05). Conclusion:1α,25 - dihydroxyvitamin D3 suppresses podocytes oc-curring EMT by inhibiting the expression of β - catenin and TGF - β which are signal transduction factors of podocytes EMT signal transduction pathway.
出处
《中国中西医结合肾病杂志》
2015年第6期486-489,共4页
Chinese Journal of Integrated Traditional and Western Nephrology
基金
福建省自然基金资助项目(No.2013J01346)