Natural emodin reduces myocardial ischemia/reperfusion injury by modulating the RUNX1/miR‑142‑3p/DRD2 pathway and attenuating inflammation

Zhang,Xuezhi; Zhang,Xuezhi; Qin,Qiaoji; Qin,Qiaoji; Lv,Xianghong; Lv,Xianghong; Wang,Yongbin; Wang,Yongbin; Luo,Feng; Luo,Feng; Xue,Li; Xue,Li

doi:10.3892/etm.2022.11681

Natural emodin reduces myocardial ischemia/reperfusion injury by modulating the RUNX1/miR‑142‑3p/DRD2 pathway and attenuating inflammation

Authors:
- Xuezhi Zhang
- Qiaoji Qin
- Xianghong Lv
- Yongbin Wang
- Feng Luo
- Li Xue
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Affiliations: Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Department of Emergency Internal Medicine, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Department of Pediatrics, The Qingdao Central Hospital, Qingdao, Shandong 266042, P.R. China, Department of Endoscopy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
Published online on: November 7, 2022 https://doi.org/10.3892/etm.2022.11681
Article Number: 745
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute myocardial infarction is one of the leading causes of death worldwide. Although timely reperfusion could attenuate myocardial ischemia injury and reduce mortality, it causes severe secondary injury to the myocardium known as myocardial ischemia/reperfusion injury (MIRI) with unmet clinical needs. Emodin has a protective effect on MIRI in rodents. However, the precise mechanism underlying its pharmacological effect remains poorly understood. Accordingly, the present study used mRNA and microRNA (miRNA) sequencing based on MIRI mouse models to determine the mechanism involved. Emodin was found to prevent MIRI and attenuate the inflammation of myocardium in the MIRI model. In addition, by using an interdisciplinary approach, the present study uncovered that emodin suppressed the runt‑related transcription factor 1 (RUNX1), which is a transcription factor of miR‑142‑3p, in either MIRI or the hypoxia/reoxygenation injury model. Furthermore, miR‑142‑3p can negatively regulate dopamine receptor D2 (DRD2), which acted as an anti‑inflammatory factor to suppress NF‑κB‑dependent inflammation and prevent MIRI. These results were demonstrated by both cellular hypoxia/reoxygenation and mouse MIRI models. Overall, the present study provided an unrevealed molecular mechanism for emodin function. Emodin could inhibit NF‑κB‑triggered inflammation in MIRI by regulating the RUNX1/miR‑142‑3p/DRD2 pathway. Therefore, the RUNX1/miR‑142‑3p/DRD2 pathway presented a novel target for MIRI treatment, and the application of emodin in clinical practice may improve the treatment of MIRI.

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