{"title":"Sigma-1受体介导的高迁移率组A1沉默减轻内质网应激诱导的卵巢颗粒细胞凋亡:体外细胞实验研究","authors":"Lile Jiang, Shujun Yang, Cuilian Zhang","doi":"10.1111/1471-0528.18081","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>To investigate the role and underlying mechanism of sigma-1 receptor (SigmaR1)/high mobility group A1 (HMGA1) in the pathogenesis of diminished ovarian reserve (DOR).</p>\n </section>\n \n <section>\n \n <h3> Design</h3>\n \n <p>In vitro cell experimental study.</p>\n </section>\n \n <section>\n \n <h3> Setting</h3>\n \n <p>The Reproductive Medical Center, People's Hospital of Zhengzhou University.</p>\n </section>\n \n <section>\n \n <h3> Sample</h3>\n \n <p>Serum, follicular fluid (FF), ovarian granulosa cells (GCs) and KGN cells.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Samples were collected from DOR patients. Endoplasmic reticulum (ER) stress was induced in the GCs using thapsigargin (TG). mRNA and protein levels were determined using reverse transcription-quantitative polymerase chain reaction and western blotting. Cell apoptosis and viability were assessed using flow cytometry and cell counting kit-8. Protein colocalization was detected via immunofluorescence. Molecular interactions were validated using co-immunoprecipitation, luciferase reporter and chromatin immunoprecipitation assays.</p>\n </section>\n \n <section>\n \n <h3> Main Outcome Measures</h3>\n \n <p>Cell viability, cell apoptosis, SigmaR1, HMGA1 and ER stress-associated mRNA levels.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>SigmaR1 expression decreased while HMGA1 expression increased in the serum, FF and GC samples of DOR patients and TG-treated GCs. TG induced ER stress and GC apoptosis; these effects were diminished by SigmaR1 overexpression or HMGA1 silencing. SigmaR1 expressed in the nuclear envelope forms a complex with gene repressor-specific protein 3 (SP3) and histone deacetylase (HDAC)1/2/3; however, TG reduced SigmaR1 in GCs and blocked the complex formation. HMGA1, a transcriptional target of SP3, was negatively modulated by the SigmaR1/SP3 complex. HMGA1 overexpression abolished the protective effect of SigmaR1 on TG-induced ER stress and GC apoptosis.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>SigmaR1 formed a SmigaR1/SP3/HDAC complex to inhibit HMGA1 transcription, alleviating ER stress and GC apoptosis and providing new therapeutic targets for DOR.</p>\n </section>\n </div>","PeriodicalId":50729,"journal":{"name":"Bjog-An International Journal of Obstetrics and Gynaecology","volume":"132 S2","pages":"120-131"},"PeriodicalIF":4.7000,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Sigma-1 Receptor-Mediated High Mobility Group A1 Silencing Alleviates Endoplasmic Reticulum Stress-Induced Ovarian Granulosa Cell Apoptosis: An In Vitro Cell Experimental Study\",\"authors\":\"Lile Jiang, Shujun Yang, Cuilian Zhang\",\"doi\":\"10.1111/1471-0528.18081\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>To investigate the role and underlying mechanism of sigma-1 receptor (SigmaR1)/high mobility group A1 (HMGA1) in the pathogenesis of diminished ovarian reserve (DOR).</p>\\n </section>\\n \\n <section>\\n \\n <h3> Design</h3>\\n \\n <p>In vitro cell experimental study.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Setting</h3>\\n \\n <p>The Reproductive Medical Center, People's Hospital of Zhengzhou University.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Sample</h3>\\n \\n <p>Serum, follicular fluid (FF), ovarian granulosa cells (GCs) and KGN cells.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Samples were collected from DOR patients. Endoplasmic reticulum (ER) stress was induced in the GCs using thapsigargin (TG). mRNA and protein levels were determined using reverse transcription-quantitative polymerase chain reaction and western blotting. Cell apoptosis and viability were assessed using flow cytometry and cell counting kit-8. Protein colocalization was detected via immunofluorescence. Molecular interactions were validated using co-immunoprecipitation, luciferase reporter and chromatin immunoprecipitation assays.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Main Outcome Measures</h3>\\n \\n <p>Cell viability, cell apoptosis, SigmaR1, HMGA1 and ER stress-associated mRNA levels.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>SigmaR1 expression decreased while HMGA1 expression increased in the serum, FF and GC samples of DOR patients and TG-treated GCs. TG induced ER stress and GC apoptosis; these effects were diminished by SigmaR1 overexpression or HMGA1 silencing. SigmaR1 expressed in the nuclear envelope forms a complex with gene repressor-specific protein 3 (SP3) and histone deacetylase (HDAC)1/2/3; however, TG reduced SigmaR1 in GCs and blocked the complex formation. HMGA1, a transcriptional target of SP3, was negatively modulated by the SigmaR1/SP3 complex. HMGA1 overexpression abolished the protective effect of SigmaR1 on TG-induced ER stress and GC apoptosis.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>SigmaR1 formed a SmigaR1/SP3/HDAC complex to inhibit HMGA1 transcription, alleviating ER stress and GC apoptosis and providing new therapeutic targets for DOR.</p>\\n </section>\\n </div>\",\"PeriodicalId\":50729,\"journal\":{\"name\":\"Bjog-An International Journal of Obstetrics and Gynaecology\",\"volume\":\"132 S2\",\"pages\":\"120-131\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-02-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bjog-An International Journal of Obstetrics and Gynaecology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/1471-0528.18081\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OBSTETRICS & GYNECOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bjog-An International Journal of Obstetrics and Gynaecology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/1471-0528.18081","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
Sigma-1 Receptor-Mediated High Mobility Group A1 Silencing Alleviates Endoplasmic Reticulum Stress-Induced Ovarian Granulosa Cell Apoptosis: An In Vitro Cell Experimental Study
Objective
To investigate the role and underlying mechanism of sigma-1 receptor (SigmaR1)/high mobility group A1 (HMGA1) in the pathogenesis of diminished ovarian reserve (DOR).
Design
In vitro cell experimental study.
Setting
The Reproductive Medical Center, People's Hospital of Zhengzhou University.
Samples were collected from DOR patients. Endoplasmic reticulum (ER) stress was induced in the GCs using thapsigargin (TG). mRNA and protein levels were determined using reverse transcription-quantitative polymerase chain reaction and western blotting. Cell apoptosis and viability were assessed using flow cytometry and cell counting kit-8. Protein colocalization was detected via immunofluorescence. Molecular interactions were validated using co-immunoprecipitation, luciferase reporter and chromatin immunoprecipitation assays.
Main Outcome Measures
Cell viability, cell apoptosis, SigmaR1, HMGA1 and ER stress-associated mRNA levels.
Results
SigmaR1 expression decreased while HMGA1 expression increased in the serum, FF and GC samples of DOR patients and TG-treated GCs. TG induced ER stress and GC apoptosis; these effects were diminished by SigmaR1 overexpression or HMGA1 silencing. SigmaR1 expressed in the nuclear envelope forms a complex with gene repressor-specific protein 3 (SP3) and histone deacetylase (HDAC)1/2/3; however, TG reduced SigmaR1 in GCs and blocked the complex formation. HMGA1, a transcriptional target of SP3, was negatively modulated by the SigmaR1/SP3 complex. HMGA1 overexpression abolished the protective effect of SigmaR1 on TG-induced ER stress and GC apoptosis.
Conclusion
SigmaR1 formed a SmigaR1/SP3/HDAC complex to inhibit HMGA1 transcription, alleviating ER stress and GC apoptosis and providing new therapeutic targets for DOR.
期刊介绍:
BJOG is an editorially independent publication owned by the Royal College of Obstetricians and Gynaecologists (RCOG). The Journal publishes original, peer-reviewed work in all areas of obstetrics and gynaecology, including contraception, urogynaecology, fertility, oncology and clinical practice. Its aim is to publish the highest quality medical research in women''s health, worldwide.