| Title: | 17β-Estradiol promotes LL37-induced rosacea-like skin inflammation via G protein-coupled estrogen receptor 30 |
| Journal: | Journal of Dermatological Science |
| Published: | 2 Jun 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40670220/ |
| DOI: | https://doi.org/10.1016/j.jdermsci.2025.05.005 |
Publication 15142
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Abstract
BACKGROUND: Rosacea is a common chronic inflammatory skin condition that predominantly affects females, though its underlying mechanisms remain unclear.</p>
OBJECTIVE: To explore the role of 17β-estradiol (E2) and the G-coupled estrogen receptor 30 (GPR30) in the pathogenesis of rosacea.</p>
METHODS: We conducted a cross-sectional analysis of UK Biobank data to investigate the association between exogenous hormone use and rosacea risk in females. Additionally, ovariectomized (OVX) LL37-induced rosacea mouse models were utilized to evaluate the effects of ovarian E2 loss and exogenous E2 supplementation. GPR30 expression was measured in rosacea skin lesions, LL37-treated mice, and HaCaT keratinocytes. The impact of GPR30 deletion on rosacea inflammation was assessed using GPR30 knockout mice. Finally, the efficacy of GPR30 inhibition or silencing in reducing inflammation was examined in LL37 or LL37 plus E2 treated mice and HaCaT cells.</p>
RESULTS: UK Biobank data revealed significant associations between oral contraceptive use (OR: 1.20; 95 % CI: 1.06, 1.37) and hormone-replacement therapy (OR: 1.31; 95 % CI: 1.18, 1.46) with increased rosacea risk. OVX mice exhibited reduced skin erythema and dermal infiltration, effects reversed by E2 supplementation, which exacerbated rosacea inflammation. GPR30 was overexpressed in rosacea lesions, LL37-treated mice, and HaCaT cells, with TFAP2C potentially mediating this effect. GPR30-deficient mice showed reduced inflammation, while GPR30 inhibition or knockdown significantly improved rosacea-like inflammation in LL37 or LL37 plus E2 treated models.</p>
CONCLUSION: Activation of the E2/GPR30 pathway plays a significant role in rosacea inflammation, and GPR30 inhibition may represent a novel therapeutic strategy for rosacea.</p>
11 Authors
- Jin Tang
- Peng Chen
- Chuchu Huang
- Wanjing Wang
- Ben Wang
- Wei Shi
- Yan Tang
- Zhili Deng
- Yiya Zhang
- Ji Li
- Dan Jian
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