HDAC4-AS1/CTCF Transcriptionally Represses HDAC4 Under Stress, Whereas HDAC4 Inhibits Stress-Induced Syncytiotrophoblast Cellular Pyroptosis by Deacetylating NLRP3 and GSDMD

IF 2.8 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Biochemistry and Function Pub Date : 2025-03-18 DOI:10.1002/cbf.70064

Juan Du, Qinghong Ji, Lihua Dong, Lanlan Wang, Gang Xin

{"title":"HDAC4-AS1/CTCF Transcriptionally Represses HDAC4 Under Stress, Whereas HDAC4 Inhibits Stress-Induced Syncytiotrophoblast Cellular Pyroptosis by Deacetylating NLRP3 and GSDMD","authors":"Juan Du, Qinghong Ji, Lihua Dong, Lanlan Wang, Gang Xin","doi":"10.1002/cbf.70064","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Our previous study reported that histone deacetylase 4 (HDAC4) expression is significantly downregulated in placental tissues of pre-eclampsia (PE) pregnancies. Cellular pyroptosis is a key event in the pathogenesis of PE that induces the release of factors into the maternal circulation. The aim of this study is to analyze the role and related molecular mechanisms of HDAC4 in PE trophoblast cell pyroptosis. Hypoxia and lipopolysaccharide (LPS)/ATP-treated immortalized human placental villous trophoblast cells HTR-8/SVneo were utilized to mimic the placental trophoblast cell state in PE. Both hypoxia and LPS/ATP treatments induced significant HTR-8/SVneo cell pyroptosis, whereas HDAC4 overexpression inhibited the induced cell pyroptosis. HDAC4 could bind to NLRP3 and GSDMD proteins, and lead to a decrease in acetylated NLRP3 and GSDMD proteins, thereby inhibiting cell pyroptosis. Hypoxia and LPS/ATP treatment significantly upregulated HDAC4-AS1 levels in HRT-8/SVneo cells. HDAC4-AS1 could bind to <i>HDAC4</i> gene promoter sequences as well as CTCF protein. HDAC4-AS1 overexpression recruited the enrichment of CTCF on <i>HDAC4</i> promoter sequences and further repressed HDAC4 transcription and expression. Targeting the transcriptional regulatory mechanism of HDAC4-AS1/HDAC4 may be able to ameliorate the clinical symptoms of PE maternal by inhibiting cellular pyroptosis in syncytiotrophoblast cells under stress.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 3","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Biochemistry and Function","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cbf.70064","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Our previous study reported that histone deacetylase 4 (HDAC4) expression is significantly downregulated in placental tissues of pre-eclampsia (PE) pregnancies. Cellular pyroptosis is a key event in the pathogenesis of PE that induces the release of factors into the maternal circulation. The aim of this study is to analyze the role and related molecular mechanisms of HDAC4 in PE trophoblast cell pyroptosis. Hypoxia and lipopolysaccharide (LPS)/ATP-treated immortalized human placental villous trophoblast cells HTR-8/SVneo were utilized to mimic the placental trophoblast cell state in PE. Both hypoxia and LPS/ATP treatments induced significant HTR-8/SVneo cell pyroptosis, whereas HDAC4 overexpression inhibited the induced cell pyroptosis. HDAC4 could bind to NLRP3 and GSDMD proteins, and lead to a decrease in acetylated NLRP3 and GSDMD proteins, thereby inhibiting cell pyroptosis. Hypoxia and LPS/ATP treatment significantly upregulated HDAC4-AS1 levels in HRT-8/SVneo cells. HDAC4-AS1 could bind to HDAC4 gene promoter sequences as well as CTCF protein. HDAC4-AS1 overexpression recruited the enrichment of CTCF on HDAC4 promoter sequences and further repressed HDAC4 transcription and expression. Targeting the transcriptional regulatory mechanism of HDAC4-AS1/HDAC4 may be able to ameliorate the clinical symptoms of PE maternal by inhibiting cellular pyroptosis in syncytiotrophoblast cells under stress.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell Biochemistry and Function 生物-生化与分子生物学

CiteScore

6.20

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Cell Biochemistry and Function publishes original research articles and reviews on the mechanisms whereby molecular and biochemical processes control cellular activity with a particular emphasis on the integration of molecular and cell biology, biochemistry and physiology in the regulation of tissue function in health and disease. The primary remit of the journal is on mammalian biology both in vivo and in vitro but studies of cells in situ are especially encouraged. Observational and pathological studies will be considered providing they include a rational discussion of the possible molecular and biochemical mechanisms behind them and the immediate impact of these observations to our understanding of mammalian biology.