Modulation of the RAC1/MAPK/ERK signalling pathway by farnesyl diphosphate synthase regulates granulosa cells proliferation in polycystic ovary syndrome

IF 4.3 3区生物学 Human Cell Pub Date : 2024-03-29 DOI:10.1007/s13577-024-01050-5

{"title":"Modulation of the RAC1/MAPK/ERK signalling pathway by farnesyl diphosphate synthase regulates granulosa cells proliferation in polycystic ovary syndrome","authors":"","doi":"10.1007/s13577-024-01050-5","DOIUrl":null,"url":null,"abstract":"<h3>Abstract</h3> <p>Polycystic ovary syndrome (PCOS) is a complex gynaecological endocrine disease that occurs in women of childbearing age. The pathogenesis of PCOS is still unclear and further exploration is needed. Here, proteomic analysis indicated that the expression of farnesyl diphosphate synthase (FDPS) protein in ovarian tissue of PCOS mice was significantly decreased. The purpose of this study is to investigate the relationship between potential biomarkers of PCOS and granulosa cells (GCs) function. The mechanisms by which FDPS affected the proliferation of granulosa cells were also explored both in vitro and in vivo. We found that knockdown of FDPS inhibited the proliferation of KGN (human ovarian granulosa cell line), while overexpression of FDPS had the opposite effect. FDPS activated Rac1 (Rac Family Small GTPase 1) activity and regulated MAPK/ERK signalling pathway, which affecting the proliferation of KGN cells significantly. In addition, treatment with the adeno-associated virus (AAV)-FDPS reverses the dehydroepiandrosterone (DHEA)-induced PCOS-phenotype in mice. Our data indicated that FDPS could regulate the proliferation of ovarian GCs by modulating MAPK/ERK (mitogen-activated protein kinase/extracellular regulated protein kinases) pathway via activating Rac1 activity. These findings suggest that FDPS could be of great value for the regulation of ovarian granulosa cell function and the treatment of PCOS.</p>","PeriodicalId":13228,"journal":{"name":"Human Cell","volume":"45 1","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s13577-024-01050-5","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}

引用次数: 0

Abstract

Polycystic ovary syndrome (PCOS) is a complex gynaecological endocrine disease that occurs in women of childbearing age. The pathogenesis of PCOS is still unclear and further exploration is needed. Here, proteomic analysis indicated that the expression of farnesyl diphosphate synthase (FDPS) protein in ovarian tissue of PCOS mice was significantly decreased. The purpose of this study is to investigate the relationship between potential biomarkers of PCOS and granulosa cells (GCs) function. The mechanisms by which FDPS affected the proliferation of granulosa cells were also explored both in vitro and in vivo. We found that knockdown of FDPS inhibited the proliferation of KGN (human ovarian granulosa cell line), while overexpression of FDPS had the opposite effect. FDPS activated Rac1 (Rac Family Small GTPase 1) activity and regulated MAPK/ERK signalling pathway, which affecting the proliferation of KGN cells significantly. In addition, treatment with the adeno-associated virus (AAV)-FDPS reverses the dehydroepiandrosterone (DHEA)-induced PCOS-phenotype in mice. Our data indicated that FDPS could regulate the proliferation of ovarian GCs by modulating MAPK/ERK (mitogen-activated protein kinase/extracellular regulated protein kinases) pathway via activating Rac1 activity. These findings suggest that FDPS could be of great value for the regulation of ovarian granulosa cell function and the treatment of PCOS.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

二磷酸法尼基合成酶对 RAC1/MAPK/ERK 信号通路的调节作用可调控多囊卵巢综合征中颗粒细胞的增殖

摘要多囊卵巢综合征（PCOS）是一种复杂的妇科内分泌疾病，多发于育龄妇女。多囊卵巢综合征的发病机制尚不清楚，需要进一步研究。蛋白质组学分析表明，多囊卵巢综合征小鼠卵巢组织中法尼酰二磷酸合成酶（FDPS）蛋白的表达量明显下降。本研究旨在探讨多囊卵巢综合征的潜在生物标志物与颗粒细胞（GCs）功能之间的关系。我们还在体外和体内探讨了 FDPS 影响颗粒细胞增殖的机制。我们发现，敲除 FDPS 会抑制 KGN（人类卵巢颗粒细胞系）的增殖，而过表达 FDPS 则会产生相反的效果。FDPS激活了Rac1（Rac家族小GTP酶1）的活性，调控了MAPK/ERK信号通路，从而显著影响了KGN细胞的增殖。此外，腺相关病毒（AAV）-FDPS还能逆转小鼠脱氢表雄酮（DHEA）诱导的多囊卵巢综合征表型。我们的数据表明，FDPS 可通过激活 Rac1 的活性，调节 MAPK/ERK（丝裂原活化蛋白激酶/细胞外调节蛋白激酶）通路，从而调节卵巢 GCs 的增殖。这些研究结果表明，FDPS 在调节卵巢颗粒细胞功能和治疗多囊卵巢综合征方面具有重要价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Human Cell 生物-细胞生物学

CiteScore

6.60

自引率

2.30%

发文量

176

期刊介绍： Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.