GPR87 protects UVB-damaged skin by coordinating antioxidant, DNA repair, and anti-inflammatory responses via Nrf2 and PI3K/AKT–NF-κB pathways
5 affiliations
- 1Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China
- 2Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
- 3Yunnan Botanee Bio-technology Group Co., Ltd., Kunming, Yunnan 650106, China
- 4Yunnan Characteristic Plant Extraction Laboratory, Yunnan Characteristic Plant Extraction Laboratory Co., Ltd., Kunming, Yunnan 650106, China
- 5China Liwa Institute of Skin Health, East China Normal University, Shanghai, 200241, China
Abstract
GPR87 has been implicated in tumorigenesis, malignant progression, and remodeling of the tumor microenvironment in various cancers; however, its role in the skin remains largely unexplored, despite its abundant expression in skin. Here, we found that UVB exposure markedly downregulated GPR87 expression in human skin tissues, HaCaT keratinocytes, and mouse skin. Importantly, genetic deletion of Gpr87 exacerbated UVB-induced skin injury in C57BL/6 mice. In keratinocytes, RNA interference–mediated knockdown of GPR87 increased reactive oxygen species (ROS) levels. Both in vivo and in vitro data further showed that GPR87 deficiency aggravated inflammatory responses and cyclobutane pyrimidine dimer (CPD) accumulation while attenuating apoptosis in skin cells. Moreover, GPR87 facilitated CPD clearance by regulating the expression and ubiquitination of XPC, a key component of the nucleotide excision repair pathway. Mechanistically, GPR87 enhances antioxidant defense by promoting Nrf2 nuclear translocation and the expression of downstream antioxidant genes. In parallel, loss of GPR87 activates the PI3K/AKT pathway and its downstream effector NF-κB. Notably, pharmacological inhibition of AKT effectively reversed the GPR87 deficiency–induced CPD accumulation and inflammatory responses. Collectively, these findings demonstrate that GPR87 protects against UVB-induced skin damage by coordinating antioxidant defense, DNA repair, and anti-inflammatory responses through Nrf2 and PI3K/AKT–NF-κB pathways, establishing GPR87 as a key endogenous factor in maintaining skin homeostasis under UVB stress. Thus, targeting GPR87 may provide a promising strategy for preventing or alleviating UVB-induced photodamage and related skin disorders.
Related
- Spartina anglica extract attenuates TNF-α/IFN-γ-induced inflammatory responses in HaCaT keratinocytes through suppression of the MAPK, NF-κB, and STAT1 signaling pathways
- Newly Synthesized S4MA Inhibits Inflammatory Responses Through STAT3/NF-κB Pathways in Human Colon Cancer HCT 116 Cells In Vitro
- Ursolic Acid in Hippophae rhamnoides L. Protects against Alcohol-Induced Hepatic Injury by Alleviating Inflammatory Response and Regulating Fas/FasL Activation
- Association of dietary total antioxidant capacity, dietary inflammatory index, and dietary phytochemical index with sarcopenia in middle-aged and older Iranian women: a case-control study
- Commercial Oat‐Based Cosmetic Ingredients Promote Antioxidant Capacity and Reduce Inflammatory Markers in Skin Cellular Stress Models: An Insight Into Molecular Mechanisms In Vitro
BibTeX
@article{zang2026gpr87,
title = {{GPR87 protects UVB-damaged skin by coordinating antioxidant, DNA repair, and anti-inflammatory responses via Nrf2 and PI3K/AKT–NF-κB pathways}},
author = {Kai Zang and Biao Guo and Jia-Hui Yu and Ruo-Yun Liu and Tang-Lin Liu and Cai-Bing Wang and Peng Xu and Yong-Yan Dang},
journal = {Zoological Research},
year = {2026},
month = sep,
doi = {10.24272/j.issn.2095-8137.2025.547},
url = {https://doi.org/10.24272/j.issn.2095-8137.2025.547},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - GPR87 protects UVB-damaged skin by coordinating antioxidant, DNA repair, and anti-inflammatory responses via Nrf2 and PI3K/AKT–NF-κB pathways
AU - Kai Zang
AU - Biao Guo
AU - Jia-Hui Yu
AU - Ruo-Yun Liu
AU - Tang-Lin Liu
AU - Cai-Bing Wang
AU - Peng Xu
AU - Yong-Yan Dang
PY - 2026
DA - 2026/09/18
JO - Zoological Research
DO - 10.24272/j.issn.2095-8137.2025.547
UR - https://doi.org/10.24272/j.issn.2095-8137.2025.547
AB - GPR87 has been implicated in tumorigenesis, malignant progression, and remodeling of the tumor microenvironment in various cancers; however, its role in the skin remains largely unexplored, despite its abundant expression in skin. Here, we found that UVB exposure markedly downregulated GPR87 expression in human skin tissues, HaCaT keratinocytes, and mouse skin. Importantly, genetic deletion of Gpr87 exacerbated UVB-induced skin injury in C57BL/6 mice. In keratinocytes, RNA interference–mediated knockdown of GPR87 increased reactive oxygen species (ROS) levels. Both in vivo and in vitro data further showed that GPR87 deficiency aggravated inflammatory responses and cyclobutane pyrimidine dimer (CPD) accumulation while attenuating apoptosis in skin cells. Moreover, GPR87 facilitated CPD clearance by regulating the expression and ubiquitination of XPC, a key component of the nucleotide excision repair pathway. Mechanistically, GPR87 enhances antioxidant defense by promoting Nrf2 nuclear translocation and the expression of downstream antioxidant genes. In parallel, loss of GPR87 activates the PI3K/AKT pathway and its downstream effector NF-κB. Notably, pharmacological inhibition of AKT effectively reversed the GPR87 deficiency–induced CPD accumulation and inflammatory responses. Collectively, these findings demonstrate that GPR87 protects against UVB-induced skin damage by coordinating antioxidant defense, DNA repair, and anti-inflammatory responses through Nrf2 and PI3K/AKT–NF-κB pathways, establishing GPR87 as a key endogenous factor in maintaining skin homeostasis under UVB stress. Thus, targeting GPR87 may provide a promising strategy for preventing or alleviating UVB-induced photodamage and related skin disorders.
SN - 2095-8137
ER -