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Archives of dermatological research
Feb 14, 2025;317 (1): 404.

Double-edged sword effect of GPX4 in skin homeostasis and diseases.

Hanzhang Xu, Li Yang, Yingli Wu, Hu Lei
Author Information
  1. Hanzhang Xu: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  2. Li Yang: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  3. Yingli Wu: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  4. Hu Lei: Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China. hulei@shsmu.edu.cn.
PMID: 39951160 DOI: 10.1007/s00403-025-03903-x

Abstract

Glutathione peroxidase 4 (GPX4) is a crucial antioxidant enzyme that plays a vital role in protecting cells from oxidative damage and lipid peroxidation. In the context of skin diseases, GPX4 serves as a key regulator of oxidative stress and inflammation, both of which are significant features of various skin conditions. By preventing lipid peroxidation and maintaining membrane integrity, GPX4 acts as a safeguard against cell death pathways, particularly ferroptosis, in skin diseases. Dysregulation of GPX4 in conditions such as dermatitis, psoriasis, and skin cancer is linked to heightened oxidative stress, inflammation, and tissue damage. Understanding the role of GPX4 and its intricate interactions in skin disease pathogenesis can aid in more effectively targeting oxidative stress and inflammation, leading to promising therapeutic interventions. This review summarizes the role of GPX4 in maintaining skin homeostasis and its involvement in disease, proposing strategies to target GPX4, including its post-translational modifications. Investigate the precise mechanism through which GPX4 influences the onset of skin diseases, and utilize GPX4 agonists or inhibitors as potential treatments.

Keywords

Ferroptosis GPX4 Glutathione peroxidase 4 Skin disease Skin homeostasis

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Grants

  1. 82170172/National Natural Science Foundation of China
  2. 82170145/National Natural Science Foundation of China
  3. ZY (2021-2023)-0208/Shanghai Municipal Commission of Health and Family Planning

MeSH Term

Humans
Phospholipid Hydroperoxide Glutathione Peroxidase
Homeostasis
Oxidative Stress
Skin
Ferroptosis
Lipid Peroxidation
Animals
Skin Diseases
Protein Processing, Post-Translational

Chemicals

Phospholipid Hydroperoxide Glutathione Peroxidase
Journal Article Review
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