2. Academic Validation
  3. Retracing from Outcomes to Causes: NRF2-Driven GSTA4 Transcriptional Regulation Controls Chronic Inflammation and Oxidative Stress in Atopic Dermatitis Recurrence

Retracing from Outcomes to Causes: NRF2-Driven GSTA4 Transcriptional Regulation Controls Chronic Inflammation and Oxidative Stress in Atopic Dermatitis Recurrence

  • J Invest Dermatol. 2024 Jun 13:S0022-202X(24)01735-4. doi: 10.1016/j.jid.2024.05.018.
Xin Ma 1,  Hang Zhao 2,  Jian-Kun Song 3,  Zhan Zhang 2,  Chun-Jie Gao 3,  Ying Luo 2,  Xiao-Jie Ding 2,  Ting-Ting Xue 2,  Ying Zhang 3,  Meng-Jie Zhang 2,  Mi Zhou 2,  Rui-Ping Wang 3,  Le Kuai 4,  Bin Li 5
Affiliations

Affiliations

  • 1 Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, 200443, China; Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
  • 2 Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 3 Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, 200443, China.
  • 4 Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China; Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: mjbubu@qq.com.
  • 5 Shanghai Skin Disease Hospital, Institute of Dermatology, School of Medicine, Tongji University, Shanghai, 200443, China; Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China. Electronic address: 18930568129@163.com.
PMID: 38879155 DOI: 10.1016/j.jid.2024.05.018
Abstract

Atopic dermatitis (AD), a chronic and recurrent inflammatory skin disorder, presents a high incidence and imposes a substantial economic burden. Preventing its recurrence remains a significant challenge in dermatological therapy due to poorly understood underlying mechanisms. In our study, we adopted a strategy of tracing the mechanisms of recurrence from clinical outcomes. We developed a mouse model of recurrent AD and applied clinically validated treatment regimens. Transcriptomic analyses revealed a pronounced enrichment in the glutathione metabolic pathway in the treated group. Through integrated bioinformatics and in vivo validation, we identified Glutathione S-transferase alpha 4 (GSTA4) as a pivotal mediator in AD recurrence. Immunohistochemical analysis demonstrated decreased GSTA4 expression in lesions from AD patients. Functionally, in vitro overexpression of GSTA4 significantly curtailed AD-like inflammatory responses and Reactive Oxygen Species (ROS) production. Moreover, we discovered that NRF2 transcriptional activity regulates GSTA4 expression and function. Our treatment notably augmented NRF2-mediated GSTA4 transcription, yielding pronounced anti-inflammatory and ROS-neutralizing effects. Conclusively, our findings implicate GSTA4 as a critical factor in the recurrence of AD, particularly in the context of oxidative stress and chronic inflammation. Targeting the NRF2-GSTA4 axis emerges as a promising anti-inflammatory and antioxidative strategy for preventing AD recurrence.

Keywords

Atopic Dermatitis; GSTA4; NRF2; Oxidative Stress; Recurrence.

Figures
Products