中国现代医学杂志2017，Vol.27Issue(1)：1-5,5.DOI:10.3969/j.issn.1005-8982.2017.01.001
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*
Effect of endoplasmic reticulum stress on expressions of FGF21 and its receptors in cardiomyocytes and its mechanism
摘要
Abstract
Objective To investigate the effect of endoplasmic reticulum stress (ERS) on the expressions of fibroblast growth factor 21 (FGF21) and its main receptors in cardiomyocytes and its mechanism. Methods ERS model was established by treating rat H9c2 cardiomyocytes with various concentrations of Tunicamycin (TM) (1, 5, 10, 20 and 50μmol/L). The cell survival rate was measured by CCK-8 assay. The expression of apoptosis-related proteins (c-caspase3, GRP78, Bax and Bcl-2), the key proteins of PERK-eIF2α-ATF4 sig-naling pathway (p-PERK, p-eIF2α and ATF4), CHOP as well as FGF21 and its main receptors (p-FGFR1 and β-Klotho) were measured by Western blot. Results Compared with the control group, TM treatment in-duced ERS in H9c2 cells, up-regulated the expression of pro-apoptosis proteins including c-caspase3, GRP78 and Bax, and reduced the level of anti-apoptosis protein Bcl-2; meanwhile it reduced cell viability rate in a dose-dependent manner. In addition, in the TM treated group the PERK-eIF2α-ATF4 signaling pathway was partly activated, which significantly induced expressions of FGF21, p-FGFR1 and β-Klotho when the concen-tration of TM was ≤10μmol/L. However, when the concentration of TM was>10 μmol/L, the expression of CHOP was significantly induced through fully-activated PERK-eIF2α-ATF4 signaling pathway, but the expres-sions of FGF21, p-FGFR1 and β-Klotho gradually decreased with the increase of ERS level. Conclusions The expressions of FGF21 and its main receptors correlate with the degree of ERS. Mild ERS (TM ≤ 10μmol/L) induces the expression of FGF21 and its main receptors in cardiomyocytes, while excessive ERS (TM >10 μmol/L) relatively reduces their expressions. The mechanism might be partly related to the regulation of PERK-eIF2α-ATF4 pathway in ERS.关键词
内质网应激/成纤维细胞生长因子21/心肌细胞Key words
endoplasmic reticulum stress/fibroblast growth factor 21/cardiomyocyte分类
医药卫生引用本文复制引用
梁平平,仲琳,龚磊,王佳慧,杨军..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*[J].中国现代医学杂志,2017,27(1):1-5,5.基金项目
国家自然科学基金（No81571636）；山东省自然科学基金 （）
