Differential effects of estradiol, raloxifene and tamoxifen on estrogen receptor expression in cultured human skin fibroblasts

Haczyński, Józef; Tarkowski, Rafał; Jarząbek, Katarzyna; Wołczyński, Sławomir; Magoffin, Denis A.; Czarnocki, Krzysztof; Ziegert, Maria; Jakowicki, J; Jakimiuk, Artur

doi:10.3892/ijmm.13.6.903

Cited by 13 publications

(11 citation statements)

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“…The presence of both ER isoforms has previously been documented in dermal fibroblasts in vitro and in the skin in vivo (Thornton et al ., 2003; Haczynski et al ., 2004; Pelletier and Ren, 2004; Yoo et al ., 2007). As according to a recent study ERα represents a predominant isoform expressed in human dermal fibroblasts (Rittie et al ., 2008), we focused on this isoform and first confirmed its expression by reverse transcription-PCR (RT-PCR) (Figure 1a) and western blot (Figure 1b).…”

Section: Resultsmentioning

confidence: 99%

Fli1 Is a Negative Regulator of Estrogen Receptor α in Dermal Fibroblasts

Hattori

Stawski

Nakerakanti

et al. 2011

Journal of Investigative Dermatology

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Estrogen is an important regulator of dermal fibroblast functions, including extracellular matrix (ECM) synthesis. Estrogen mediates its effects through estrogen receptors (ERs), ERα and ERβ; however, regulation of ERs in dermal fibroblasts remains poorly understood. Friend leukemia integration factor 1 (Fli1), a member of the Ets transcription factor family, has been shown to play a pivotal role in regulation of the ECM genes in dermal fibroblasts. The aim of this study was to examine a possible interaction between Fli1 and estrogen pathways, focusing on ERα. We show that treatment of human dermal fibroblasts with transforming growth factor-β (TGF-β) increases ERα protein and mRNA levels. Similarly, ERα expression was increased in response to small interfering RNA (siRNA)-mediated depletion of Fli1, suggesting that Fli1 is a mediator of the TGF-β effects on ERα expression. Accordingly, we showed that Fli1 binds to the most proximal region of the ERα promoter, and dissociates from the promoter upon TGF-β treatment. An inverse correlation between Fli1 and ERα expression levels was confirmed in cultured skin fibroblasts obtained from Fli1+/− mice and in the skin of Fli1+/− mice in vivo. This study supports a role of Fli1 as a negative regulator of the ERα gene in dermal fibroblasts.

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Section: Resultsmentioning

confidence: 99%

Fli1 Is a Negative Regulator of Estrogen Receptor α in Dermal Fibroblasts

Hattori

Stawski

Nakerakanti

et al. 2011

Journal of Investigative Dermatology

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“…Both ER␣ and ER␤ are expressed in human epidermal keratinocytes and dermal fibroblasts, and their natural ligand, estrogen, has profound influence on the skin (Haczynski et al, 2004;Walker and Korach, 2004). It is important to note that estrogen has been shown to decrease aging and wrinkling of the skin when used therapeutically (Wolff et al, 2005).…”

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confidence: 99%

Estrogen Receptor β Is a Novel Therapeutic Target for Photoaging

Chang¹,

Wang²,

Oh³

et al. 2010

Mol Pharmacol

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One of the many harmful factors faced by the skin is solar UV radiation, which damages skin by inducing chronic low-grade inflammation through increased expression of proinflammatory cytokines, metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). Estrogen receptors (ERs) ␣ and ␤ are ligand-dependent transcription factors that are expressed in skin, and an ER␤ agonist has previously shown efficacy in vivo in models of pain and inflammation. Because ER␤ does not carry the breast and uterine proliferation liabilities of ER␣, we decided to explore the possibility of using ER␤ as a target for photoaging. We show that ER␤-selective compounds suppressed the expression of cytokines and MMPs in activated keratinocytes and fibroblast-based in vitro models of photoaging. Furthermore, in activated dermal fibroblasts, ER␤-selective compounds also inhibited COX-2. These activities of ER␤ ligands in skin cells correlated with the expression levels of ER␤ and showed reversal by treatment with a potent synthetic ER antagonist. Furthermore, the pharmacology of ER␤-selective compound was observed in wild-type but not in skin cells obtained from ER␤ knockout mice. Finally, we demonstrate that a synthetic ER␤ agonist inhibited UV-induced photodamage and skin wrinkle formation in a murine model of photoaging. Therefore, the potential of an ER␤ ligand to regulate multiple pathways underlying the cause of photoaging suggests ER␤ to be a novel therapeutic target for the prevention and treatment of photoaging.Photoaging results from the repetitive exposure of skin to damaging effects of solar UV radiation and is characterized by wrinkles, laxity, dryness, and mottled pigmentation. In recent years, some of the molecular mechanisms underlying the cause of photoaging have been described. The process of photoaging involves three cell types, namely keratinocytes, fibroblasts, and infiltrating neutrophils (Fisher et al., 2002;Rijken et al., 2005;Makrantonaki and Zouboulis, 2007). Within minutes of UVB radiation exposure, epidermal keratinocytes show an increased activation of transcription factors, activator protein 1 (AP-1), and nuclear factor-B (NF-B), resulting in high expression of matrix metalloproteinases (MMPs) and proinflammatory cytokines (Fisher et al., 1996). These cytokines and a UVA component of the UV radiation in turn activate dermal fibroblasts to secrete MMPs, which damage the collagen component of the dermal extracellular matrix (Fagot et al., 2004). Cytokines and chemotactic factors that are secreted by skin cells also recruit neutrophilic granulocytes to the dermis. These neutrophils further degrade dermal extracellular matrix by secreting MMPs and elastases, thus contributing to UV-mediated dermal collagen and elastin degradation (Rijken et al., 2005). Repetitive UV exposure leads to the accumulation of partially degraded extracellular matrix components in the dermis, resulting in wrinkle appearance. Therefore, a number of pathways and processes involved in photoaging could be targeted by potential therapeutic a...

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“…As ER-α and ER-β are normally expressed by fibroblasts and in skin biopsies [20,21], we examined the effects of the combination of hormonal incubation and irradiation in a cell line of a male donor. Radiation as well as different chemical and biological agents induce changes toward growth arrest with morphological characteristics of senescence in surviving colony-forming fibroblasts [23].…”

Section: Discussionmentioning

confidence: 99%