School of Clinical Medicine, Chifeng University, Hongshan, Chifeng, Inner Mongolia, China.
Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Haikou, China.
Peptides. 2022 Jun;152:170774. doi: 10.1016/j.peptides.2022.170774. Epub 2022 Feb 24.
Endoplasmic reticulum stress (ERS) plays an important role in the process of myocardial hypertrophy in diabetic cardiomyopathy (DCM). Irisin, a novel cytokine, has been found to protect against cardiac diastolic dysfunction in DCM. We aimed to investigate the role of irisin in cardiac hypertrophy and to elucidate the underlying mechanisms.
H9c2 cells were induced with 33 mM glucose to construct a cardiac hypertrophy cell model, which was then treated with irisin in the presence or absence of the ERS inducer tunicamycin (TM). The cell surface area was measured by FITC-phalloidin staining. The atrial natriuretic peptide levels were detected by an enzyme-linked immunosorbent assay. Furthermore, the expression of the ERS-related proteins, P-PERK, PERK, IRE1α and GRP78, was detected by western blotting.
Irisin significantly reduced myocardial hypertrophy and suppressed high glucose (HG)-induced oxidative stress. Meanwhile, the protective effect of irisin on cardiomyoblasts was reversed by the ERS inducer, TM. Additionally, we detected ERS-associated signaling pathway proteins and found that irisin significantly reduced the protein expression levels of GRP78 and p-PERK/PERK.
These results suggest that irisin ameliorates HG-induced cardiac hypertrophy by inhibiting ERS.
内质网应激（ERS）在糖尿病心肌病（DCM）心肌肥厚过程中发挥重要作用。新型细胞因子鸢尾素已被发现可预防 DCM 中的舒张性心脏功能障碍。我们旨在研究鸢尾素在心肌肥厚中的作用，并阐明其潜在机制。
用 33mM 葡萄糖诱导 H9c2 细胞构建心肌肥厚细胞模型，然后用鸢尾素处理，同时存在或不存在 ERS 诱导剂衣霉素（TM）。用 FITC-鬼笔环肽染色测量细胞表面积。通过酶联免疫吸附试验检测心房利钠肽水平。此外，通过 Western blot 检测 ERS 相关蛋白 P-PERK、PERK、IRE1α 和 GRP78 的表达。
鸢尾素可显著减轻心肌肥厚，并抑制高糖（HG）诱导的氧化应激。同时，ERS 诱导剂 TM 逆转了鸢尾素对心肌细胞的保护作用。此外，我们检测了 ERS 相关信号通路蛋白，发现鸢尾素可显著降低 GRP78 和 p-PERK/PERK 的蛋白表达水平。
这些结果表明，鸢尾素通过抑制 ERS 改善 HG 诱导的心肌肥厚。
