The Expression of Histone Deacetylase 1, But Not Other Class I Histone Deacetylases, Is Significantly Increased in Endometriosis

Samartzis, Eleftherios Pierre; Noske, Aurelia; Samartzis, Nicolas; Fink, Daniel; Imesch, Patrick

doi:10.1177/1933719113488450

Cited by 43 publications

(40 citation statements)

References 30 publications

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“…First, a global H3K4 and H3K9 hypomethylation in endometriotic lesions has been reported recently [ 37 ]. In addition, global H3 hypoacetylation as well as HDAC1 overexpression also have been reported [ 17 , 38 , 39 ]. While selective inhibition of prostaglandin E2 receptors EP2 and EP4 is shown to have many desirable therapeutic effects [ 40 ], it has no effect on LSD1 expression in endometriotic lesions [ 41 ].…”

Section: Introductionmentioning

confidence: 99%

Tranylcypromine, a lysine-specific demethylase 1 (LSD1) inhibitor, suppresses lesion growth and improves generalized hyperalgesia in mouse with induced endometriosis

Sun¹,

Ding

Liu

et al. 2016

Reprod Biol Endocrinol

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BackgroundGrowing evidence indicates that endometriosis is an epigenetic disease. Encouragingly, histone deacetylases (HDACs) and DNA methyltransferases have been shown to be promising targets by numerous in vitro studies. However, only a few studies have shown promising effects of HDAC inhibition in preclinical studies in endometriosis. While lysine-specific demethylase 1 (LSD1) is recently found to be aberrantly expressed in endometriosis, and that the treatment of endometriotic stromal cells with tranylcypromine (TC), an LSD1 inhibitor, significantly reduced cellular proliferation, cell cycle progression, and invasiveness, the in vivo effect of TC treatment is currently lacking. This study sought to evaluate the effect of TC in a mouse model of endometriosis.MethodsForty-seven female C57BL/6 mice were used in this experimentation. All mice, except those randomly selected to form Sham surgery (M) and specificity control (S) groups, received an endometriosis-inducing surgery. Group S was set up mainly to ensure that the reduced generalized hyperalgesia in mice treated with TC is not due to any possible analgesic effect of TC, but rather resulting from the treatment effect specific to endometriosis. Two weeks after the surgery, mice that received surgery were further divided randomly into 3 groups: 1) untreated group (U); 2) low-dose TC group (L); 3) high-dose TC group (H). Group S received the same treatment as in group H. Two weeks after treatment, all mice were sacrificed and their ectopic endometrial tissues were harvested and analyzed by immunohistochemistry analysis. Hotplate test was administrated to all mice before the induction, treatment and sacrifice. Lesion size, hotplate latency, immunoreactivity against markers of proliferation, angiogenesis, H3K4 methylation, and of epithelial-mesenchymal transition (EMT).ResultsTC treatment significantly and substantially reduced the lesion size and improved generalized hyperalgesia in a dose-dependent fashion in mice with induced endometriosis. In addition, TC treatment resulted in reduced immunoreactivity to biomarkers of proliferation, angiogenesis, and H3K4 methylation, leading to arrested EMT and lesion growth.ConclusionIn light of our previously reported reduced cellular proliferation, cell cycle progression and invasiveness resulting from the LSD1 inhibition in in vitro studies, our data strongly suggest that LSD1 is a promising therapeutic target for endometriosis.Trial registrationNot applicable.

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Section: Introductionmentioning

confidence: 99%

Tranylcypromine, a lysine-specific demethylase 1 (LSD1) inhibitor, suppresses lesion growth and improves generalized hyperalgesia in mouse with induced endometriosis

Sun¹,

Ding

Liu

et al. 2016

Reprod Biol Endocrinol

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“…It has been reported that the levels of HDAC1 and/or HDAC2, two of the most abundant HDACs in human cells, were deregulated in endometriotic stromal cells. While one study reported that both HDAC1 and HDAC2 were upregulated in endometriotic stromal cells, two other studies reported the upregulation of HDAC1 and HDAC2 . Nevertheless, the expression of HDAC1 and HDAC2 were induced by the steroid hormones, 17β‐estradiol and progesterone, a notion that is consistent with the central role of steroid hormones in the development of endometriosis (Figure ).…”

Section: Alteration Of the Histone Code In Endometriosismentioning

confidence: 52%

Epigenetic regulation of the pathological process in endometriosis

Hsiao

Tsai

2017

Reprod Medicine & Biology

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BackgroundEndometriosis is one of the most common gynecological diseases that greatly compromises the quality of life in affected individuals. A growing body of evidence shows that the remodeling of retrograde endometrial tissues to the ectopic endometriotic lesions involves multiple epigenetic alterations, such as DNA methylation, histone modification, and microRNA expression.MethodsThis article retrospectively reviewed the studies that were related to the epigenetic regulatory factors that contribute to the development and maintenance of endometriosis. A literature search was performed in order to collect scientific articles that were written in English by using the key words of “endometriosis,” “epigenetics,” “DNA methylation,” “histone modification,” and “microRNA.”ResultsEpigenetic modifications, including DNA methylation, histone modification, and microRNA expression, are involved in the pathogenesis of endometriosis. These epigenetic players are regulated or tuned by microenvironmental cues, such as locally produced estradiol, proinflammatory cytokines, and hypoxic stress, and reciprocally regulate the process or response to those stimuli.ConclusionUnderstanding the molecular mechanisms that underlie these epigenetic regulatory processes would shed light on the etiology and/or progression of endometriosis and facilitate the development of novel therapeutic strategies.

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“…This observation was confirmed by the reported higher expression of HDAC1 and HDAC2 genes and lower levels of SIRT1 in the endometriotic lesions of affected women in comparison with normal endometrium. Moreover, in ectopic implants, the loss of HDAC expression modulation by estrogen and progesterone was reported [128,129,136]. Studies concerning histone modification are still scarce and heterogeneous in results, method, and study design.…”

Section: Epigenetic Histone Modificationsmentioning

confidence: 99%

Genetic, Epigenetic, and Steroidogenic Modulation Mechanisms in Endometriosis

Zubrzycka

Zubrzycki

Perdas

et al. 2020

JCM

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Endometriosis is a chronic gynecological disease, affecting up to 10% of reproductive-age women. The exact cause of the disease is unknown; however, it is a heritable condition affected by multiple genetic, epigenetic, and environmental factors. Previous studies reported variations in the epigenetic patterns of numerous genes known to be involved in the aberrant modulation of cell cycle steroidogenesis, abnormal hormonal, immune and inflammatory status in endometriosis, apoptosis, adhesion, angiogenesis, proliferation, immune and inflammatory processes, response to hypoxia, steroidogenic pathway and hormone signaling are involved in the pathogenesis of endometriosis. Accumulating evidence suggest that various epigenetic aberrations may contribute to the pathogenesis of endometriosis. Among them, DNA methyltransferases, histone deacetylators, and non-coding microRNAs demonstrate differential expression within endometriotic lesions and in the endometrium of patients with endometriosis. It has been indicated that the identification of epigenetic differences within the DNA or histone proteins may contribute to the discovery of a useful prognostic biomarker, which could aid in the future earlier detection, timely diagnosis, and initiation of a new approach to the treatment of endometriosis, as well as inform us about the effectiveness of treatment and the stage of the disease. As the etiology of endometriosis is highly complex and still far from being fully elucidated, the presented review focuses on different approaches to identify the genetic and epigenetic links of endometriosis and its pathogenesis.

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The Expression of Histone Deacetylase 1, But Not Other Class I Histone Deacetylases, Is Significantly Increased in Endometriosis

Cited by 43 publications

References 30 publications

Tranylcypromine, a lysine-specific demethylase 1 (LSD1) inhibitor, suppresses lesion growth and improves generalized hyperalgesia in mouse with induced endometriosis

Tranylcypromine, a lysine-specific demethylase 1 (LSD1) inhibitor, suppresses lesion growth and improves generalized hyperalgesia in mouse with induced endometriosis

Epigenetic regulation of the pathological process in endometriosis

Genetic, Epigenetic, and Steroidogenic Modulation Mechanisms in Endometriosis

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