p38 MAPK信号途径参与大鼠系膜细胞MMP2表达  

p38 MAPK signal transduction pathways involved in MMP2 expression in rat mesangial cells

作　　者：史伟[1] 刘双信[1] 梁馨苓[1] 单志新[2] 王文健[1] 叶智明[1] 梁永正[1] 

机构地区：[1]广东省人民医院肾内科,广东广州510080 [2]广东省人民医院中心实验室,广东广州510080

出　　处：《基础医学与临床》2005年第11期1037-1041,共5页Basic and Clinical Medicine

基　　金：广东省自然科学基金(020426);广东省重点攻关项目科研基金(30701007);广东省卫生厅基金(A2001044)(A2005036)

摘　　要：目的探讨系膜细胞中调节MMP2表达的信号通路。方法鼠系膜细胞培养,分别加入酪氨酸激酶抑制剂(Herbimycin A),p38MAPK抑制剂(SB203580),MEK抑制剂(U0126),ERK抑制剂(PD098059),PI3K抑制剂(Y294002),用酶谱法分析MMP2酶活性、用RT-PCR及Western方法从基因及蛋白水平,观察阻断剂对MMP2表达的影响。结果酪氨酸激酶抑制剂、MEK抑制剂、ERK抑制剂及PI3K抑制剂对MMP2酶活性、mRNA及蛋白水平无影响,在72 h p38 MAPK抑制剂SB203580抑制MMP2活性25%。在48 h当SB203580浓度分别为10、20、30及40μmol/L时,系膜细胞中MMP2的抑制率分别为7.2%、13.5%、21.3%及28%。结论大鼠系膜细胞中p38MAPK信号传导途径参与了MMP2的表达,并且p38 MAPK抑制剂SB203580对MMP2的抑制有剂量依赖性。Objective To investigate the signal transduction pathways involved in matrix metalloproteinases-2 in rat mesangial cell. Methods Rat mesangial cells were cultured using routine. The effects of p38 inhibitor SB203580, MEK inhibitor U0126, extracellular signal-regulated kinase（ERK） inhibitor PD098059, phosphatidylinositaol 3-kinase（PI3K） inhibitor LY294002, and tyrosine kinase inhibitor herbimycin A on production and secretion of MMP-2 in mesangial cell were determined by gelatin zymography, semiquantitative reverse transcriptase （RT-PCR） and Western blot. Results The p38 inhibitor SB203580 depressed MMP-2 production by about 25 % at a 72-hour culture （ P 〈 0.05）, but MEK inhibitor U0126, extracellular signal-regulated kinase （ERK） inhibitor PD098059, phosphatidylinositaol 3-kinase （ PI3 K） inhibitor LY294002, and tyrosine kinase inhibitor herbimycin A didn＇t affect the activity, protein and gene expression of MMP-2 in masangial cell. When concentrations of SB203580 were 10,20, 30, and 40 μmol/L in different groups, the ratios of MMP-2 depression were 7.2%, 13.5%, 21.3%, and 28% at 48 hours respectively. Conclusion p38 MAPK signal transduetion pathways may be involved in the production of matrix metalloproteinases-2, and have dose-dependen regulation production of MMP-2 in mesangial cell.

关 键 词：基质金属蛋白酶 信号传导途径 系膜细胞 P38 MAPK 

分 类 号：R692[医药卫生—泌尿科学]