期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

ERK1／2MAPK通路在甲羟戊酸促进人类肾小球系膜细胞增殖中的作用

Effects of ERK1/2 MAPK pathway in the Mevalonic acid on promotion of proliferation of human mesangial cells
下载PDF
导出
摘要 目的探讨甲羟戊酸（MVA）促进人类肾小球系膜细胞（HMC）增殖中，细胞外信号调控蛋白激酶1／2（ERK1／2）丝裂原激活蛋白激酶（MAPK）通路的作用及机制。方法将体外培养的HMC根据不同的处理因素分为正常对照组、MVA组（100nmol／L）、MVA（100nmol／L）加PD98059（50μmol／L）组即MVA加PD组，以不含干预因素正常培养细胞为对照组，分别于干预后12、24h收集各组细胞，应用Western blot法检测P-ERK1／2、Bcl-2、Bax蛋白的表达。结果①p-ERK1／2蛋白的表达：MVA组在各个时间点的表达均明显上调，且随时间延长，蛋白表达增加（P〈0．05）；而MVA加PD组在各个时间点的表达均无明显变化（P〉0．05）。②Bcl-2与Bax蛋白的表达：MVA组与MVA加PD组在各个时间点Bcl-2蛋白表达均明显上调，且随时间延长表达增加（P〈0．05）；而各个时间点Bax蛋白的表达均明显下调（P〈0．05）；但随时间延长，MVA组表达下降（P〈0．05），而MVA加PD组表达下降不明显（P〉0．05）；③Bcl-2／Bax：MVA组与MVA加PD组在各个时间点均升高，且随时间延长Bcl-2／Bax升高（P〈0．05）；而在各个时间点，MVA加PD组较MVA组Bcl-2／Bax明显下降（P〈0．05）。结论MVA可通过Ⅱ水1／2信号转导通路促进HMC增殖；ERK1／2信号转导通路促进HMC增殖可通过上调Bcl-2及下调Bax的表达，并最终通过上调Bcl-2／Bax而实现。 Objective To investigate the effects and mechanism of extracellular signal-regulated mitogen activated protein kinase1/2（ERK1/2 MAPK） pathway in the Mevalonic acid （MVA） on promotion of proliferation of human mesangial cells（HMC）. Method The human mesangial cells were cultured in vitro. These cells were stimulated with MVA（ 100 nmol/L）and MVA（ 100 nmol/L）plus PD98059（50 umol/L）. The cells without being interfered were selected as control groups. The protein expression of p-ERK1/2,Bcl-2, Bax were examined by western blotting. Results Compared with control group, the protein expression of p-ERK1/2 upregulated after MVA intervention and increased in time-dependent manner （ P 〈 0. 05）, while it showed no significant difference after MVA plus PE08059. Compared with control groups, The protein expression of Bcl-2 upregulated and Bax downregulated after MVA intervention and MVA plus PE08059, the ratio of Bcl-2 and of Bax was sifnificantly increased（ P〈0. 05）. But compared with MVA groups,the protein expression of Bcl-2 and the ratio of Bcl-2 and Bax decreased and Bax increased to some extent after MVA plus PD98059. Conclusions MVA exerts its proliferation effect ,at least in part,by activation of ERKI/2 MAPK pathway. The pathway make HMC proliferate by upregulating the protein expression of Bcl-2 and downregulating the protein expression of Bax,and by upregulating the ratio of Bcl-2 and Bax at last.
作者 王清华 李荣山
机构地区 山西医科大学第二临床医院肾内科
出处 《临床肾脏病杂志》 2007年第3期132-134,共3页 Journal Of Clinical Nephrology
基金 山西省科技攻关项目（No2006031089-2）
关键词 甲羟戊酸 细胞外信号调节蛋白MAP激酶类 系膜细胞 肾小球 增殖 Mevalonic acid Extracellular signal-regulated MAP kinases Mesangial cell, kidney glomerulus Proliferation
分类号 R692.6 [医药卫生—泌尿科学]
  • 相关文献

参考文献7

  • 1孙小鹉,王清华,张文军,徐磊,李荣山.甲羟戊酸对人类肾小球系膜细胞增殖的影响[J].山西医科大学学报,2006,37(7):707-709. 被引量：1
  • 2Grandallano G, Biswas P, Choudhury GG, et al. Simvastatin inhibits PDGF-induced DNA synthesis in human glomerular mesangial cells. Kidney Int, 1993, 44: 503-509.
  • 3冯惠平,崔炜,都军,郝玉明.洛伐他汀对醛固酮诱导大鼠心肌成纤维细胞增殖的影响[J].中国新药与临床杂志,2005,24(1):24-28. 被引量：13
  • 4Boulton TG, Nye SH, Robbins DJ, et al. ERKs: a family of protein-serine/threonine kinases that are activated and tyrosine phosphorylatedin response to insulin and NGF. Cell, 1991, 65: 663-675.
  • 5Widmann C, Gibosn S, Jarpe MB, et al. Mitogen activated protein kinase: conservation of a three kinase module from yeast to human. Physiol Rev, 1999,79:143-1802.
  • 6Oltvai Z, Milliman C, Korsmeyer SJ . Bcl-2 heterodimerizes in viv125I-labeled antipyrinewith a conserved homolog, Bax, that accelerates programmed cell death. Cell, 1993,74 : 609-616.
  • 7Stupack DG, Cheresh DA. Get a ligand, get a life: integrins, signali-ng and cell survival. J Cell Sci, 2002, 115 (Pt 19) : 3729- 3737.

二级参考文献17

  • 1冯惠平,崔炜,都军,郝玉明.洛伐他汀对醛固酮诱导大鼠心肌成纤维细胞增殖的影响[J].中国新药与临床杂志,2005,24(1):24-28. 被引量：13
  • 2PATEL R, NAGUEH SF, TSYBOULEVA N, et al. Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy[J]. Circulation, 2001, 104(3) : 317-324.
  • 3BAUERSACHS J, GALUPPO P, FRACCAROLLO D, et al. Improvement of left ventricular remodeling and function by hydroxymethylglutaryl coenzyme a reductase inhibition with cerivastatin in rats with heart failure after myocardial infarction [ J ]. Circulation,2001, 104(9) : 982-985.
  • 4ODA H, KASISKE BL, ODONNELL MY, et al. Effects of lovastatin on expression of cell cycle regulatory proteins in vascular smooth muscle cells[ J]. Kidney Int Suppl, 1999, 71: S 202-S205.
  • 5STOCKAND JD, MESZAROS JG. Aldosterone stimulates proliferation of cardiac fibroblasts by activating Ki-RasA and MAPKI/2 signaling[J]. Am J Physiol Heart Circ Physiol, 2003, 284( 1 ):H176-H184.
  • 6LAUFS U, KILTER H, KONKOL C, et al. Impact of HMG CoA reductase inhibition on small GTPases in the heart[ J]. Cardiovasc Res, 2002 , 53(4) : 911-920.
  • 7TAKEDA Y, YONEDA T, DEMURA M, et aL. Cardiac aldostetone production in genetically hypertension rats[ J ]. Hypertension,2000,36(4) : 495-500.
  • 8UNLU S, CLUNN G, SCHACITIER M, et od. Action of an HMGCoA reductase inhibitor, lovastatin, on apoptosis of untransformed and ts-SV40 transformed human smooth muscle ceils derived from saphenous vein[J]. J Cardiovasc Pharmacol, 2001, 38(2) : 161-173.
  • 9NISHIMURA M, TANAKA T, YASUDA T, et al. Collagen secretion and growth of mesangial ceils require geranylgeranylpyrophosphate[J]. Kidney Int, 1999, 55(2) : 520-528.
  • 10BOUTERFA HL, SATTELMEYER V, CZUB S, et al. Inhibition of Ras farnesylation by lovastatin leads to downregulation of proliferation and migration in primary cultured human glioblastoma cell [J]. Anticancer Res, 2000, 20(4) : 2761-2771.

共引文献12

临床肾脏病杂志
2007年 第3期

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