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Theranostics 2022; 12(15):6626-6645. doi:10.7150/thno.77243 This issue Cite

Review

Comprehensive overview of Nrf2-related epigenetic regulations involved in ischemia-reperfusion injury

Jun Zhang^1*, Wanqian Pan^1*, Yue Zhang^1*, Mingyue Tan¹, Yunfei Yin¹, Yuanmei Li³, Lei Zhang¹, Lianhua Han¹, Jiaxiang Bai^1,2✉, Tingbo Jiang^1✉, Hongxia Li^1✉

1. Department of Cardiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, China.
2. Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou 215000, China.
3. Department of Cardiology, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Suzhou 215000, Jiangsu, China.
*These authors contributed equally to this work.

✉ Corresponding authors: Hongxia Li, Department of Cardiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P. R. China. E-mail: shrimpedu.cn; Tingbo Jiang, Department of Cardiology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P. R. China. E-mail: 18906201122cn; Jiaxiang Bai, Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P. R. China. E-mail: jxbai1995com. More

Abstract

Ischemic disease is a class of diseases in which an organ is ischemic due to vascular occlusion, a major contributor to death and disability worldwide. However, when the blood flow is restored, more severe damage occurs than ischemia alone and is known as ischemic-reperfusion injury (IRI). During reperfusion, the imbalance between the production of reactive oxygen species (ROS) and buffering capacity of the antioxidant defense system results in cell damage and death. Nuclear factor E2-related factor 2 (Nrf2) significantly affects antioxidant stress damage. The function of Nrf2 in the pathological process of IRI has been widely discussed, but the impact of epigenetic modifications associated with Nrf2 remains unclear. This article provides a comprehensive overview of the role and mechanism of Nrf2-related epigenetic modifications in the IRI of various organs, including the brain, heart, liver, and kidney. In addition, we summarize agonists that may target epigenetic regulation of Nrf2, which may be beneficial in seeking more effective strategies to improve IRI.

Keywords: epigenetic modifications, ischemic-reperfusion injury, Nrf2, oxidative stress, therapy

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