Differential involvement of estrogen receptorα and estrogen receptorβ in the healing promoting effect of estrogen in human keratinocytes
Open accessAbstract
Estrogen affects proliferation and migration of different skin components, thus influencing wound healing processes. The human keratinocyte cell line NCTC 2544 has been used to examine the effects of estrogen, dissect its mechanism of action and characterize receptor subtypes involved. Western blot and immunocytochemical analyses confirmed the expression of estrogen receptors (ERs) α and β, with prevalence in the nuclear and extranuclear compartment, for ERα and ERβ respectively. Treatment with 10 nM 17β-estradiol (17β-E 2 ) and the ERα and ERβ selective agonists, 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT; 100 nM), and diarylpropionitrile (DPN; 1 nM) produced a slight but significant increase in cell proliferation, as by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and bromodeoxyuridine incorporation assays, only after a long-term treatment (96 h). Analysis of cell migration by a scratch wound assay showed that 17β-E 2 (10 nM) accelerated migration between 5 and 24 h after scratching, an effect confirmed by the transwell migration assay. PPT and DPN elicited similar effects. Pre-treatment with the mitogen-activated protein kinase inhibitor, U0126 (1 μM), abolished the ability of 17β-E 2 and DPN, but not of PPT, to accelerate wound closure. TGF-β1 (10 ng/ml) produced a similar positive effect on wound closure and the TGF-β1 receptor antagonist, SB431542 (10 μM), reduced the ability of 17β-E 2 and PPT to accelerate cell migration, but did not modify DPN effect. It is suggested that estrogen positively affects in vitro wound healing by stimulating cell proliferation after long-term exposure but mainly by accelerating cell migration within a few hours from treatment. Selective activation of ERβ may result in favorable stimulation of wound healing without any increase of transforming growth factor-β1 production.
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ERβ plays a critical role in wound healing.
“ERβ has been shown to play a critical role in wound healing37,38.”
From Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells (2020) · cites this paper as [37]
ERβ is important in wound healing.
“and so is ERβ37,38 in wound healing”
From Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells (2020) · cites this paper as [37]
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- Authors
- Merlo, S., Frasca, G., Canonico, P. L., & Sortino, M. A.
- Affiliations
- Università degli Studi del Piemonte Orientale “Amedeo Avogadro” (IT)
- University of Catania (IT)
- Corresponding author
- Sortino, Maria Angela
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2008-11-13
- Volume
- 200
- Issue
- 2
- Pages
- 189-197
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2150763460
- Cited by
- 53
- References
- 30
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 1 · 2020: 5 · 2019: 1 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 4 · 2013: 5
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- Journal of Endocrinology (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- estrogen receptor alpha, estrogen receptor beta, wound healing, keratinocytes, estradiol, cell proliferation, cell migration, TGF-β1, mitogen-activated protein kinase, diarylpropionitrile, selective estrogen receptor agonists
- MeSH terms
- Cell Line, Cell Movement, Estradiol, Estrogens, Humans, Nitriles, Phenols, Propionates, Pyrazoles, Wound Healing, Keratinocytes, Gene Expression, Estrogen Receptor alpha, Estrogen Receptor beta, Cell Proliferation, In Vitro Techniques
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