1. 6-Gingerol relieves myocardial ischaemia/reperfusion injury by regulating lncRNA H19/miR-143/ATG7 signaling axis-mediated autophagy
- Author
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Qiu-Yu Qin, Meng-Jie Wang, Pan Lu, Guo-wei Qin, and Xiangwei Lv
- Subjects
Male ,0301 basic medicine ,Catechols ,Myocardial Reperfusion Injury ,Caspase 3 ,Autophagy-Related Protein 7 ,Cell Line ,Pathology and Forensic Medicine ,Flow cytometry ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Autophagy ,medicine ,Animals ,Viability assay ,Molecular Biology ,Caspase-9 ,biology ,medicine.diagnostic_test ,Chemistry ,Cell Biology ,medicine.disease ,Cell biology ,Mice, Inbred C57BL ,Blot ,MicroRNAs ,030104 developmental biology ,Apoptosis ,030220 oncology & carcinogenesis ,biology.protein ,RNA, Long Noncoding ,Fatty Alcohols ,Reperfusion injury ,Signal Transduction - Abstract
Myocardial ischemia/reperfusion injury (MIRI) causes severe damage in cardiac tissue, thereby resulting in a high rate of mortality. 6-Gingerol (6-G) is reported to play an essential role in alleviating MIRI. However, the underlying mechanism remains obscure. This study was intended to explore the potential mechanism by which 6-G functions. Q-PCR was employed to quantify the relative RNA levels of long noncoding RNA (lncRNA) H19 (H19), miR-143, and ATG7, an enzyme essential for autophagy, in HL-1 cells. Western blotting, immunofluorescence, and immunohistochemistry were employed for protein evaluation in cultured cells or mouse tissues. Cell viability, cytotoxicity, and apoptosis were analysed by CCK-8, LDH, and flow cytometry assays, respectively. The binding sites for miR-143 were predicted using starBase software and experimentally validated through a dual-luciferase reporter system. Here, we found that 6-G elevated cellular H19 expression in hypoxia/reoxygenation (H/R)-treated HL-1 cells. Moreover, 6-G increased Bcl-2 expression but reduced cleaved caspase 3 and caspase 9 protein levels. Mechanistically, H19 directly interacted with miR-143 and lowered its cellular abundance by acting as a molecular sponge. Importantly, ATG7 was validated as a regulated gene of miR-143, and the depletion of miR-143 by H19 caused an increased in ATG7 expression, which in turn promoted the autophagy process. Last, mouse experiments highly supported our in vitro findings that 6-G relieves MIRI by enhancing autophagy. The H19/miR-143/ATG7 axis was shown to be critical for the function of 6-G in relieving MIRI.
- Published
- 2021