黄健, 陈松, 杨静, 闵亚丽. 阿利吉仑抑制转化生长因子-β1诱导肾小管上皮细胞转分化的作用研究[J]. 临床肾脏病杂志, 2018, 18(8): 466-470. DOI: 10.3969/j.issn.1671-2390.2018.08.004
    引用本文: 黄健, 陈松, 杨静, 闵亚丽. 阿利吉仑抑制转化生长因子-β1诱导肾小管上皮细胞转分化的作用研究[J]. 临床肾脏病杂志, 2018, 18(8): 466-470. DOI: 10.3969/j.issn.1671-2390.2018.08.004
    HUANG Jian, CHEN Song, YANG Jing, MIN Ya-li. Effects of Aliskiren on transdifferentiation induced by TGF-β1 in human renal tubular epithelial cells[J]. Journal of Clinical Nephrology, 2018, 18(8): 466-470. DOI: 10.3969/j.issn.1671-2390.2018.08.004
    Citation: HUANG Jian, CHEN Song, YANG Jing, MIN Ya-li. Effects of Aliskiren on transdifferentiation induced by TGF-β1 in human renal tubular epithelial cells[J]. Journal of Clinical Nephrology, 2018, 18(8): 466-470. DOI: 10.3969/j.issn.1671-2390.2018.08.004

    阿利吉仑抑制转化生长因子-β1诱导肾小管上皮细胞转分化的作用研究

    Effects of Aliskiren on transdifferentiation induced by TGF-β1 in human renal tubular epithelial cells

    • 摘要: 目的 探讨阿利吉仑对转化生长因子-β1(TGF-β1)诱导人近端肾小管上皮细胞(HKC)转分化的作用及其对血小板源性生长因子-BB (PDGF-BB)、血管内皮生长因子(VEGF)表达的影响。方法 体外培养HKC,然后分为4组。阴性对照组HKC未做任何处理,阿利吉仑组HKC以阿利吉仑(1.0×10-7 mmol/L)单独处理24 h,TGF-β1组HKC以TGF-β1(8 ng/ml)单独处理24 h,研究组HKC以同一浓度的TGF-β1加阿利吉仑共同处理24 h。应用免疫细胞组织化学、逆转录-聚合酶链反应(RT-PCR)观察阿利吉仑对TGF-β1诱导的HKC转分化的作用及对α-平滑肌肌动蛋白(α-SMA)、PDGF-BB、VEGF表达的影响。结果 阴性对照组HKC有少量的PDGF-BB和α-SMA表达,有微量的VEGF表达。在TGF-β1干预24 h后HKC有大量α-SMA、PDGF-BB的表达,与阴性对照组有显著差异(P<0.05);有少量的VEGF的表达,与阴性对照组无差异(P>0.05)。阿利吉仑单独作用于HKC 24 h后α-SMA、VEGF及PDGF-BB的表达与阴性对照组无显著差异(P>0.05)。TGF-β1加阿利吉仑组比TGF-β1组诱导的HKC α-SMA、PDGF-BB的表达明显降低(P<0.05),VEGF的表达无显著差异(P>0.05)。结论 TGF-β1诱导肾小管上皮细胞转分化24 h可使PDGF-BB的表达明显增加,但对VEGF无明显改变。阿利吉仑对TGF-β1诱导的肾小管上皮细胞转分化可能通过下调PDGF-BB的表达起抑制作用,但对VEGF的影响尚不明确,为阿利吉仑在肾间质纤维化的临床应用提供理论依据。

       

      Abstract: Objective To explore Aliskiren on transdifferentiation of renal tubular epithelial cells (HKC) induced by TGF-β1 and to evaluate its effect on platelet derived growth factor(PDGF-BB)、vascular endothelialgrowth factor (VEGF) expressing change.Methods HKC were divided into four groups and cultured for 24 hours in different conditions separately:Serum free as control, Treated with Aliskiren(1.0×10-7 mmol/L);Treated with TGF-β1(8 ng/ml); Treated with TGF-β1 plus Aliskiren in the same concentration. The expression of α-SMA was assessed with RT-PCR, the expression of PDGF-BB、VEGF was assessed with RT-PCR and immunohistochemistry after 24 hours.Results There are little expression of PDGF-BB, VEGF and α-SMA mRNA in control group. Compared with the control group, The expression of PDGF-BB and α-SMA mRNA was markedly increased in HCK cultured with TGF-β1 group (P<0.05),which were suppressed significantly in HKC cultured with TGF-β1 plus Aliskiren group (P<0.05). but there are no significant changes in the expression of VEGF between different groups(P>0.05).Conclusions Aliskiren may inhibit transdifferentiation of tubular epithelial cells induced by TGF-β1 and reduce the expression of PDGF-BB. The inhibition of Aliskiren on transdifferentiation of tubular epithelial cells may be related to the down-regulation of PDGF-BB. It is not very clear on the effect of the expression of VEGF.

       

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