期刊文献+

地塞米松对马兜铃酸诱导的人肾小管上皮-间充质转化的作用及可能机制 被引量:1

The effect and mechanism of dexamethasone on AA induced epithelial-mesenchymal transition in HKC cells
下载PDF
导出
摘要 目的探讨地塞米松(Dex)对马兜铃酸诱导的肾小管上皮-间充质转化(EMT)的影响及可能机制。方法体外培养的人肾小管上皮细胞(HKC)分为阴性对照组、马兜铃酸(AA,10μg/ml)作用组、Dex(100μmol/L)作用组、AA(10μg/ml)+无水乙醇(100μmol/L)组、AA(10μg/ml)+Dex(100、10、1、0.1、0.01μmol/L)共同作用组,培养细胞48h,应用激光共聚焦显微镜(CFMS)观察α-平滑肌肌动蛋白(α-SMA)、E-钙黏素(E-cadherin)的表达,采用Real-timePCR和WesternBlot方法检测α-SMA、E-cadherin、p-Smad3、转化生长因子-β1(TGF-β1)、Smad7mRNA和蛋白的表达。结果 AA作用48h后,CFMS观察发现HKC细胞E-cadherin表达减弱而α-SMA表达增强;地塞米松干预后,E-cadherin表达逐渐增强而α-SMA表达减弱,且呈剂量依赖性。Real-timePCR、WesternBlot结果均显示,与阴性对照组相比,AA组α-SMA、p-Smad3、TGF-β1mRNA和蛋白表达水平均显著增强,E-cadherin、Smad7mRNA和蛋白的表达均减弱(P<0.05)。同AA作用组比较,AA+Dex共同作用组随Dex剂量增加,α-SMA、p-Smad3、TGF-β1mRNA和蛋白的表达逐渐减弱,E-cadherin、Smad7mRNA和蛋白的表达逐渐增强(P<0.05),而无水乙醇却无此作用。结论 Dex可抑制AA诱导HKC细胞发生EMT,并同时下调EMT过程中TGF-β1和p-Smad3的表达、上调Smad7分子的表达,提示TGF-β1/Smad下调可能是Dex抑制EMT发生的机制之一。 Objective To explore the effect and mechanism of dexamethasone (Dex)on AA induced epithelial-mesenchymal transition in HKC ceils. Methods Cultured HKC cells were divided into five groups: negative control group, incubated with AA(10 μg/ml) alone group, incubated with Dex (100 μmol/L) alone group, incubated with AA (10 μg/ml) group and absolute ethanol (100 μmol/L)group, or incubated with AA (10 μg/ml) and Dex group at different concentrations (100, 10, 1, 0.1, 0.01 μmol/L) for 48 h. Confocal microscope was used to detect expressions of α-SMA and E-cadherin. The mRNA and protein expressions of α-SMA, E-cadherin, TGF-β1, p-Smad 3 and Smad 7 were assessed with real-time PCR and western Blot, respectively. In the other experiment, HKC cells were incubated with AA (10 μg/ml) in the absence or presence of Dex (100 μmol/L), respectively. The mRNA and protein expressions of α-SMA, E-cadherin, p-Smad 3, TGF-β1 and Smad 7 were assessed with real-time PCR and western Blot at different time points respectively. Results As revealed by confocal microscope, AA inhibited E-cadherin expression and enhanced α-SMA expression in HKC cells. Dex reversed AA-induced inhibition of E-cadherin and promotion of α-SMA expressions. Real-time PCR and western Blot showed that mRNA and protein expressions of α-SMA, p-Smad 3 and TGF-β1 significantly decreased, E-cadherin and Smad 7 significantly increased in ceils incubated with AA and Dex, compared with that treated with AA alone (P 〈 0.05). There was no significant difference between the group of AA alone and the group treated with AA and absolute ethanol for mRNA and protein expression of α-SMA, p-Smad 3 and TGF-β1 in HKC cells. Conclusions The results of the present study suggest that Dex may partially inhibit AA-induced EMT of HKC cells in vitro, which is probably contributed to the repression of TGF-β1 and p-Smad 3, up-regulation of Smad 7 expressions. Further study is needed.
出处 《北京医学》 CAS 2012年第4期305-309,I0002,共6页 Beijing Medical Journal
基金 国家自然科学基金(30570854)
关键词 地塞米松 肾小管上皮-间充质转化 马兜铃酸 转化生长因子-Β1 SMAD Dexamethasone (Dex) Epithelial-mesenchymal transition (EMT) Aristolochic acid (AA) Transforming growth faetor-β1 (TGF-β1) Smad
  • 相关文献

参考文献16

  • 1陈文,谌贻璞,李安,程虹,董葆,邹万忠,赵世萍,付桂香.马兜铃酸肾病的临床与病理表现[J].中华医学杂志,2001,81(18):1101-1105. 被引量:124
  • 2Iwano M,Neilson EG. Mechanisms of tubulointerstitial fibrosis[J].Current Opinion in Nephrology and Hypertension,2004.279-284.
  • 3Rees AJ. The role of infiltrating leukocytes in progressive renal disease:implications for therapy[J].Nephrology,2006.348-349.
  • 4Sean EK,Cockwell P. Macrophages and progressive tubulointerstitial disease[J].Kidney International,2005.437-455.
  • 5López-Novoa JM,Nieto MA. Inflammation and EMT:an alliance towards organ fibrosis and cancer progression[J].EMBO Mol Med,2009.303-314.
  • 6Zhou L,Fu P,Huang XR. Mechanism of chronic aristolochic acid nephropathy:role of Smad3[J].American Journal of Physiology-Renal Physiology,2010.F1006-F1017.
  • 7王会玲,张金元,黄健.甘草酸和泼尼松对慢性马兜铃酸肾病大鼠肾脏组织病理及超微病理改变的影响[J].中国中西医结合杂志,2007,27(1):45-49. 被引量:10
  • 8Doerner AM,Zuraw BL. TGF-betal induced epithelial to mesenchymal transition (EMT) in human bronchial epithelial cells is enhanced by IL-1beta but not abrogated by corticosteroids[J].Respiratory Research,2009.100-114.doi:10.1186/1465-9921-10-100.
  • 9Iu MF,Kaji H,Sowa H. Dexamethasone suppresses Smad3 pathway in osteoblastic cells[J].Journal of Endocrinology,2005.131-138.
  • 10Kalluri R,Neilson EG. Epithelial-mesenchymal transition and its implications for fibrosis[J].Journal of Clinical Investigation,2003.1776-1784.

二级参考文献20

  • 1王会玲,张金元,万晨旭,周巍,朱丽娟.马兜铃酸对肾小管上皮细胞释放ET、Ang-Ⅱ的影响及甘草酸干预作用的实验研究[J].上海中医药杂志,2004,38(9):47-49. 被引量:12
  • 2王会玲,张金元.甘草酸对马兜铃酸致肾小管上皮细胞损害保护作用的初步研究[J].中国中西医结合肾病杂志,2005,6(4):200-203. 被引量:18
  • 3Vanherweghem JI., Depierreux M. Tielemans C, et al.Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs. Lancet,1993,341 :387-391.
  • 4Krumme B, Endmeir R, Vanhaelen M, et al. Reversible Fanconi syndrome after ingestion of a Chinese herbal"remedy" containing aristolochic acid. Nephol Dial Transplant, 2001,40:296-300.
  • 5Vanherweghem JL, Abramowicz D. Tielemans C, et al.Effects of steroids on the progression of renal failure in chronic interstitial renal fibrosis:a pilm study in Chinese herbs nephropathy. Am J Kidney Dis, 1996, 27:209-215.
  • 6Bennett JC, Plum F. Approach to the patient with renal diseases. In: Cecil's Textbook of Medicine. 20th ed.Philadelphia: Sanunder Company WB, 1996. 185-186.
  • 7Debelle FD,Nortier JL,Eric G,et al.Aristolochic acid induce chronic renal failure with interstitial fibrosis in salt-depleted rats.J Am Soc Nephrol 2002; 13(2):431-436.
  • 8Vanherwegham JL,Abramowicz D,Tielemans C,et al.Effects of steroids on the progression of renal failure in chronic interstitial renal fibrosis:a pilot study in Chinese herbs nephropathy.Am J Kidney Dis 1996; 27 (2):209.
  • 9叶志斌,崔若蓝.服木通煎液引起肾脏损害1例[J].中国中药杂志,1997,22(9):570-571. 被引量:31
  • 10张贞丽,李宝国,韩莉.薄层扫描测定母乳灵冲剂中马兜铃酸的含量[J].中草药,1997,28(12):725-726. 被引量:3

共引文献132

同被引文献76

  • 1周斌,张培建.胆管上皮细胞的生理及其与胆管疾病的相关性[J].中国普通外科杂志,2007,16(7):681-683. 被引量:9
  • 2Greenburg G,Hay ED. Epithelia suspended in col-lagengels can lose polarity and express characteris-tics of migrating mesenchymal cells[J]. J Cell Biol,1982, 95(1): 333 — 339.
  • 3Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition [J]. J Clin Invest, 2009,119(6): 1420-1428.
  • 4Wendt MK,Allington TM, Schiemann WP. Mech-anisms of the epithelial-mesenchymal transition byTGF-beta[J]. Future Oncol, 2009 . 5(8): 1145 —1168.
  • 5Barrallo-Gimeno A, Nieto MA, The Snail genes asinducers of cell movement and survival : Implicationsin development and cancer[J]. Development, 2005.132(14) : 3151-3161.
  • 6Gonzalez-Moreno 〇,Lecanda J, Green JE, et al.VEGF elicits epithelial-mesenchymal transition(EMT) in prostate intraepithelial neoplasia (PIN)-like cells via an autocrine loop [J]. Exp Cell Res,2010,316(14) : 554-567.
  • 7Cho HJ, Baek KE, Saika S,et al. Snail is requiredfor transforming growth factor-beta induced epithe-lial-mesenchymal transition by activating PI3 ki-nase/ Aktsignal pathway[J]. Biochem Biophys ResCommun, 2007 . 353(2) : 337 — 343.
  • 8Xu SY,Li J,Geng MY. The signal transductionand drug development of epithelial-mesenchymaltransition[J]. Chin Pharmacol Bull, 2008,24(9):1131-1134.
  • 9Kuroda N,Guo L,Miyazaki E,et al. The appear-ance of myofibroblasts and the disappearance ofCD34-positive stromal cells in the area adjacent toxanthogranulomatous foci of chronic cholecystitis[J]. Histol HistopathoU 2005,20(1) : 127—133.
  • 10Bose SK, Meyer K,Di Bisceglie AM,et al. Hepa-titis C virus induces epithelial-mesenchymal transi-tion in primary human hepatocytes [ J ]. J Virol,2012,86(24) : 13621 — 13628.

引证文献1

二级引证文献16

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部