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Updated: Aug 5, 2026
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Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
Heat Stress Promotes Fibroblast-Derived WNT5A Secretion Through m6A Modification to Activate Melanogenesis
Yuanyuan Wan1, Yaqing Wen1, Yushan Zhang1
1Department of Dermatology, Third Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|July 27, 2026
Summary
Heat stress promotes skin repigmentation by upregulating WNT5A via METTL3-mediated m6A modification. This mechanism enhances melanogenesis and offers potential for treating hypopigmentation disorders.
Area of Science:
- Dermatology
- Molecular Biology
- Epigenetics
Background:
- Global warming intensifies heat stress, impacting skin and potentially causing hyperpigmentation.
- Mechanisms linking heat stress to skin pigmentation changes are not fully understood.
Purpose of the Study:
- To investigate the molecular mechanisms by which heat stress influences skin pigmentation.
- To explore the potential of heat-induced pathways for treating hypopigmentary conditions like vitiligo.
Main Methods:
- Investigated heat stress effects on mouse skin and vitiligo lesions.
- Analyzed WNT5A expression and regulation in dermal fibroblasts (FB) using METTL3 and m6A modification pathways.
- Examined WNT5A's role in melanocytes (MC) and human skin explants, including downstream signaling via β-catenin and FZD10.
Main Results:
- Heat stress induced repigmentation in vitiligo and melanogenesis in mouse skin.
- Heat stress upregulated WNT5A via METTL3-mediated m6A modification in FBs, with stability regulated by YTHDC1.
- WNT5A treatment increased melanin in MCs and skin explants, activating β-catenin and FZD10; FZD10 knockdown blocked these effects.
Conclusions:
- Heat stress promotes melanogenesis through fibroblast-derived WNT5A, regulated by METTL3/YTHDC1-dependent m6A methylation.
- This pathway highlights a novel mechanism in heat-induced skin pigmentation.
- Thermotherapy shows promise for treating hypopigmentary diseases.
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