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A role for estrogen receptor-α and estrogen receptor-β in collagen biosynthesis in mouse skin
Margaret Markiewicz1, Sergey Znoyko, Lukasz Stawski
1Medical University of South Carolina, Charleston, SC, USA. markiewi@musc.edu
Abstract:
Hormonal regulation of the dermal collagenous extracellular matrix has a key role in maintaining proper tissue homeostasis. However, the factors and pathways involved in this process are not fully defined. This study investigated the role of estrogen receptors (ERs) in the regulation of collagen biosynthesis in mice lacking either ERα or ERβ. Collagen content was significantly increased in the skin of ERα(-/-) mice, as measured by acetic acid extraction and the hydroxyproline assay, and correlated with the decreased levels of matrix metalloproteinase (MMP)-15 and elevated collagen production by ERα(-/-) fibroblasts. In contrast, collagen content was decreased in the skin of ERβ(-/-) mice, despite markedly increased collagen production by ERβ(-/-) fibroblasts. However, expression of several MMPs, including MMP-8 and -15, was significantly elevated, suggesting increased degradation of dermal collagen. Furthermore, ERβ(-/-) mice were characterized by significantly reduced levels of small leucine proteoglycans, lumican (Lum), and decorin (Dcn), leading to defects in collagen fibrillogenesis and possibly less stable collagen fibrils. ERα(-/-) mice also exhibited fibrils with irregular structure and size, which correlated with increased levels of Lum and Dcn. Together, these results demonstrate distinct functions of ERs in the regulation of collagen biosynthesis in mouse skin in vivo.
Insights
Estrogen receptors (ERs) play distinct roles in skin collagen. Estrogen receptor alpha (ERα) deficiency increases collagen, while ERβ deficiency decreases it, impacting tissue structure and homeostasis.
Area of Science:
- Dermatology
- Endocrinology
- Molecular Biology
- Extracellular Matrix Research
Background:
- Hormonal regulation of the dermal extracellular matrix is crucial for skin homeostasis.
- The specific roles of estrogen receptors (ERs) in regulating collagen biosynthesis remain incompletely understood.
Purpose of the Study:
- To investigate the distinct roles of estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in regulating collagen biosynthesis and dermal structure in mice.
Main Methods:
- Analysis of collagen content in the skin of ERα knockout (ERα(-/-)) and ERβ knockout (ERβ(-/-)) mice using acetic acid extraction and hydroxyproline assay.
- Quantification of matrix metalloproteinases (MMPs) and small leucine proteoglycans (lumican and decorin).
- Assessment of collagen fibril structure and fibroblast collagen production.
Main Results:
- ERα(-/-) mice showed increased skin collagen content, decreased MMP-15, and elevated fibroblast collagen production.
- ERβ(-/-) mice exhibited decreased skin collagen content despite increased fibroblast collagen production, with elevated MMPs (MMP-8, MMP-15) suggesting increased degradation.
- ERβ(-/-) mice had reduced lumican and decorin, leading to collagen fibrillogenesis defects, while ERα(-/-) mice showed irregular collagen fibrils associated with increased lumican and decorin.
Conclusions:
- Estrogen receptor alpha and beta have distinct and opposing roles in regulating collagen biosynthesis and dermal extracellular matrix integrity in mouse skin.
- ERα appears to promote collagen accumulation, whereas ERβ influences collagen degradation and fibril organization through proteoglycan regulation.
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