内质网应激对心肌细胞FGF21及其受体表达的影响和机制研究

发布时间：2018-04-12 15:34

本文选题：内质网应激 + 成纤维细胞生长因子　；参考：《中国现代医学杂志》2017年01期

【摘要】：目的探讨内质网应激(ERS)对心肌细胞成纤维细胞生长因子21(FGF21)及其主要受体表达的影响和机制。方法在大鼠H9c2心肌细胞中加入不同浓度的衣霉素(TM)(1、5、10、20和50μmol/L)复制ERS模型,利用活细胞计数法试剂盒检测细胞存活率。Western blot检测凋亡相关蛋白(C-caspase3、GRP78、Bax、Bcl-2)和PERK-e IF2α-ATF4信号通路相关蛋白(p-PERK、p-e IF2α、ATF4),CHOP蛋白,FGF21及其主要受体(p-FGFR1和β-Klotho)的表达。结果与对照组比较,TM处理组诱导H9c2细胞发生ERS,提高促凋亡蛋白C-caspase3、GRP78、Bax的表达,减少抗凋亡蛋白Bcl-2的表达,并以浓度依赖形式降低细胞的存活率。此外,当TM浓度≤10μmol/L时,TM处理组可以部分激活PERK-e IF2α-ATF4信号通路,诱导FGF21、p-FGFR1、β-Klotho的表达;当TM浓度10μmol/L时,TM处理组完全激活PERK-e IF2α-ATF4信号通路,诱导CHOP的表达,而FGF21、p-FGFR1及β-Klotho表达却随TM浓度的增加而逐渐降低。结论 FGF21及其主要受体的表达与ERS程度有关,轻微的ERS(TM浓度≤10μmol/L)诱导心肌细胞FGF21及其受体的表达,而严重的ERS(TM浓度10μmol/L)则相对降低FGF21及其受体的表达,其机制可能与PERK-e IF2α-ATF4信号通路在ERS中的调控有关。
[Abstract]:Objective to explore the effect of endoplasmic reticulum stress (ERS) on myocardial apoptosis of fibroblast growth factor 21 (FGF21) and its main effect and mechanism of expression of receptors. Methods with different concentrations of H9c2 in rat myocardial cells in tunicamycin (TM) (1,5,10,20 and 50 mol/L) to establish ERS model, using cell counting method assay for cell survival rate of.Western blot detection of apoptosis related proteins (C-caspase3, GRP78, Bax, Bcl-2) and PERK-e IF2 alpha -ATF4 signal pathway related proteins (p-PERK, P-E, IF2 alpha, ATF4), CHOP protein, FGF21 and its receptor (p-FGFR1 and beta -Klotho) expression. Results compared with the control group, TM group of H9c2 cells induced by ERS, improve the pro apoptotic protein C-caspase3, GRP78, the expression of Bax, reduce the expression of anti apoptotic protein Bcl-2, and in a concentration dependent decrease cell survival rate. In addition, when the concentration of TM is less than or equal to 10 mol/L, TM group can activate PER K-e IF2 alpha -ATF4 signal pathway induced by FGF21, p-FGFR1, -Klotho expression; when the concentration of TM 10 mol/L, TM group PERK-e IF2 a fully activated -ATF4 pathway, expression induced by CHOP and FGF21, the expression of p-FGFR1 and beta -Klotho was gradually reduced with the increase of TM concentration and FGF21 and on. The main receptor expression is correlated with the degree of ERS, mild ERS (TM concentration less than or equal to 10 mu mol/L) expression of myocardial cells induced by FGF21 and its receptor, and severe ERS (TM concentration 10 mol/L) was markedly decreased the expression of FGF21 and its receptor regulation, its mechanism may be related to PERK-e IF2 a -ATF4 signaling pathway in ERS.

【作者单位】：滨州医学院临床学院;青岛大学医学院附属烟台毓璜顶医院心内科;青岛大学医学院附属烟台毓璜顶医院生物芯片实验室;青岛大学医学院附属烟台毓璜顶医院中心实验室;
【基金】：国家自然科学基金(No:81571636) 山东省自然科学基金(No:ZR2015HM058)
【分类号】：R54

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