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Histone demethylase KDM4A and KDM4B expression in granulosa cells from women undergoing in vitro fertilization.

ABSTRACT: PURPOSE:To assess expression of the histone demethylases KDM4A and KDM4B in granulosa collected from women undergoing oocyte retrieval and to determine if expression was related to pregnancy outcome. METHODS:Cumulus and mural granulosa cells were obtained from women undergoing oocyte retrieval. KDM4A and KDM4B mRNA expression was determined by qRT-PCR. KDM4A and KDM4B proteins were immunohistochemically localized in ovarian tissue sections obtained from archival specimens. RESULTS:KDM4A and KDM4B protein was localized to oocytes, granulosa cells, and theca and luteal cells in ovaries from reproductive-aged women. KDM4A and KDM4B mRNA expression was overall higher in cumulus compared to mural granulosa. When comparing granulosa demethylase gene expression, KDM4A and KDM4B mRNA expression was higher in both cumulus and mural granulosa from not pregnant patients compared to patients in the pregnant-live birth group. CONCLUSIONS:Histone demethylases KDM4A and KDM4B mRNA are differentially expressed in cumulus and mural granulosa. Expression of both KDM4A and KDM4B mRNA was lower in cumulus granulosa and mural granulosa from pregnant compared to not pregnant patients. These findings suggest that altered expression of histone demethylases may impact epigenetic changes in granulosa cells associated with pregnancy.

SUBMITTER: Krieg AJ

PROVIDER: S-EPMC6029998 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Histone demethylase KDM4A and KDM4B expression in granulosa cells from women undergoing in vitro fertilization.

Krieg Adam J AJ Mullinax Sarah R SR Grimstad Frances F Marquis Kaitlin K Constance Elizabeth E Hong Yan Y Krieg Sacha A SA Roby Katherine F KF

Journal of assisted reproduction and genetics 20180314 6

<h4>Purpose</h4>To assess expression of the histone demethylases KDM4A and KDM4B in granulosa collected from women undergoing oocyte retrieval and to determine if expression was related to pregnancy outcome.<h4>Methods</h4>Cumulus and mural granulosa cells were obtained from women undergoing oocyte retrieval. KDM4A and KDM4B mRNA expression was determined by qRT-PCR. KDM4A and KDM4B proteins were immunohistochemically localized in ovarian tissue sections obtained from archival specimens.<h4>Resu ...[more]

PMID: 29536385

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Project description:PurposeAsthma is one of the most common obstructive pulmonary diseases worldwide. Epigenetic alterations, including DNA methylation and histone modifications, have been reported to contribute to asthma pathogenesis. Since the inflammation mediator and remodeling trigger, IL-13, is known to play a central role in the pathophysiology of asthma, this study was aimed to identify novel IL-13-regulated epigenetic modifiers in asthma that may contribute to subepithelial fibrosis.MethodsPublicly available transcriptomic datasets from Gene Expression Omnibus (GEO) were used to identify differentially expressed genes on an epigenetic level upon IL-13 exposure in lung fibroblasts. Bronchial fibroblasts isolated from healthy and asthmatic individuals were assessed for the gene and protein expression levels of the identified gene at baseline and upon IL-13 treatment using qRT-PCR and western blotting, respectively. Its subcellular localization and tissue distribution were examined in bronchial fibroblasts as well as bronchial biopsies by immunofluorescence and immunohistochemical analysis, respectively.ResultsBioinformatic analysis revealed the differential expression of the histone demethylase JMJD2B/KDM4B, a well-known epigenetic modulator that leads to the demethylation of different lysine residues on histones, in IL-13-treated lung fibroblasts. The baseline expression levels of JMJD2B were higher in asthmatic fibroblasts and in bronchial biopsies in comparison to healthy ones. There was also an increase in JMJD2B activity as evidenced by the demethylation of its downstream target, H3K36me3. Furthermore, IL-13 stimulation induced JMJD2B expression and further demethylation of H3K36me3 in asthmatic fibroblasts. This was accompanied by increased translocation of JMJD2B into the nucleus.ConclusionThis study highlights the novel pathological involvement of the histone demethylase JMJD2B/KDM4B in asthmatic airway fibroblasts that are regulated by IL-13. Clinical implications. Given that there is no single therapeutic medicine to effectively treat the various subtypes of asthma, this study provides promising insights into JMJD2B as a new therapeutic target that could potentially improve the treatment and management of asthma.

Dataset Information

Histone demethylase KDM4A and KDM4B expression in granulosa cells from women undergoing in vitro fertilization.

Publications

Histone demethylase KDM4A and KDM4B expression in granulosa cells from women undergoing in vitro fertilization.

Similar Datasets

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