HDAC5 inhibits ovarian angiogenesis in dehydroepiandrosterone-induced mouse model of polycystic ovary syndrome.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2022-01-01 Epub Date: 2022-09-20 DOI:10.5603/FHC.a2022.0024

Ying Wang, Yu Wang, Yao Chen, Qianqian Gao, Lihui Hou, Xiaoling Feng

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引用次数: 0

Abstract

Introduction: Abnormal ovarian angiogenesis is a common feature of polycystic ovary syndrome (PCOS), a typical endocrine disorder affecting women of reproductive age. Histone deacetylase 5 (HDAC5) has been documented as a suppressor of angiogenesis. The aim of this study was to explore the effect of HDAC5 on ovarian angiogenesis in a PCOS mouse model.

Material and methods: PCOS was induced in female C57BL/6 mice by 20-day administration of dehydroepiandrosterone (DHEA). HDAC5 was over-expressed in PCOS mice by corresponding adenovirus injection. In total, 120 mice were used in this study. Western-blotting, real-time PCR, hematoxylin and eosin staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemical staining, flow cytometry, and co-immunoprecipitation were respectively used to evaluate the effect of HDAC5 on PCOS mice.

Results: PCOS ovaries showed a compensatory increase in HDAC5 expression, while HDAC5 over-expression alleviated abnormalities in ovarian morphology and serum hormone levels after PCOS modeling. HDAC5 inhibited ovarian angiogenesis in PCOS mice by regulating angiogenesis-related factors, such as VEGFA, platelet-derived growth factors B and D (PDGFB/D), and angiopoietins 1 and 2 (ANGPT1/2) and CD31. HDAC5 over-expression decreased levels of reactive oxygen species (ROS) and malondialdehyde, while promoting activities of catalase and superoxide dismutase in ovaries of PCOS mice, suggesting its suppressive effects on oxidative stress, an inducer of uncontrolled angiogenesis. Moreover, HDAC5 suppressed activation of angiogenesis-related HIF-1α/VEGFA/VEGFR2 signaling in PCOS ovaries partly via inhibiting VEGFR2 acetylation.

Conclusions: This study reveals the protective role of HDAC5 in PCOS by inhibiting ovarian angiogenesis and provides a molecular candidate for PCOS therapy in the future.

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HDAC5抑制多囊卵巢综合征小鼠脱氢表雄激素模型卵巢血管生成。

卵巢血管生成异常是多囊卵巢综合征(PCOS)的共同特征，多囊卵巢综合征是一种典型的影响育龄妇女的内分泌疾病。组蛋白去乙酰化酶5 (HDAC5)已被证明是血管生成的抑制因子。本研究旨在探讨HDAC5对PCOS小鼠卵巢血管生成的影响。材料与方法:用脱氢表雄酮(DHEA)诱导雌性C57BL/6小鼠PCOS 20 d。通过相应的腺病毒注射在PCOS小鼠中过表达HDAC5。本研究共使用120只小鼠。分别采用Western-blotting、real-time PCR、苏木精和伊红染色、酶联免疫吸附试验(ELISA)、免疫组织化学染色、流式细胞术和免疫共沉淀法评价HDAC5对PCOS小鼠的作用。结果:PCOS卵巢HDAC5表达代偿性升高，而HDAC5过表达可减轻PCOS造模后卵巢形态及血清激素水平的异常。HDAC5通过调节血管生成相关因子，如VEGFA、血小板源性生长因子B和D (PDGFB/D)、血管生成素1和2 (ANGPT1/2)和CD31，抑制PCOS小鼠卵巢血管生成。HDAC5过表达可降低PCOS小鼠卵巢中活性氧(ROS)和丙二醛的水平，同时促进过氧化氢酶和超氧化物歧化酶的活性，提示其对氧化应激有抑制作用，氧化应激是血管生成失控的诱导因子。此外，HDAC5通过抑制VEGFR2乙酰化抑制PCOS卵巢中血管生成相关的HIF-1α/VEGFA/VEGFR2信号的激活。结论:本研究揭示了HDAC5通过抑制卵巢血管生成对PCOS的保护作用，为未来PCOS治疗提供了分子候选物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.