在重症急性胰腺炎中,m6A 激活的 BACH1 通过表观遗传抑制 HSPB1 而加剧铁蛋白沉积症

IF 3.5 4区 医学 Q2 CHEMISTRY, MEDICINAL Drug Development Research Pub Date : 2024-09-16 DOI:10.1002/ddr.22256
Fawei Zhou, Dezhong Li, Chang Liu, Can Li, Kaili Li, Lu Shi, Fachun Zhou
{"title":"在重症急性胰腺炎中,m6A 激活的 BACH1 通过表观遗传抑制 HSPB1 而加剧铁蛋白沉积症","authors":"Fawei Zhou,&nbsp;Dezhong Li,&nbsp;Chang Liu,&nbsp;Can Li,&nbsp;Kaili Li,&nbsp;Lu Shi,&nbsp;Fachun Zhou","doi":"10.1002/ddr.22256","DOIUrl":null,"url":null,"abstract":"<p>Severe acute pancreatitis (SAP) is characterized by acute inflammation of the pancreas. The transcription factor BTB and CNC homology 1 (BACH1) has been implicated in various biological processes, including oxidative stress, apoptosis, and cell cycle regulation. However, its involvement in the pathogenesis of SAP remains relatively understudied. In the present work, our data demonstrated that BACH1 level was significantly increased in SAP patients, cellular, and animal models, while heat shock protein B1 (HSPB1) expression was weakened. Mechanistic assays validated that BACH1 acted as a transcriptional inhibitor of HSPB1. Moreover, HPDE6-C7 cells were stimulated with cerulein (Cer) and LPS to mimic the pathological stages of SAP in vitro. Depletion of BACH1 remarkably improved cell survival and alleviated the oxidative stress, ferroptosis, and inflammatory responses in SAP cell models. However, these changes were dramatically reversed upon co-inhibition of HSPB1. Animal findings confirmed that loss of BACH1 decreased pancreatic injury, inflammatory responses, and ferroptosis, but these effects were weakened by HSPB1 silence. Overall, these findings elucidate that the overexpression of BACH1 favors the ferroptosis and inflammation by transcriptionally inhibiting HSBP1, thereby exacerbating SAP progression.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"m6A-activated BACH1 exacerbates ferroptosis by epigenetic suppression HSPB1 in severe acute pancreatitis\",\"authors\":\"Fawei Zhou,&nbsp;Dezhong Li,&nbsp;Chang Liu,&nbsp;Can Li,&nbsp;Kaili Li,&nbsp;Lu Shi,&nbsp;Fachun Zhou\",\"doi\":\"10.1002/ddr.22256\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Severe acute pancreatitis (SAP) is characterized by acute inflammation of the pancreas. The transcription factor BTB and CNC homology 1 (BACH1) has been implicated in various biological processes, including oxidative stress, apoptosis, and cell cycle regulation. However, its involvement in the pathogenesis of SAP remains relatively understudied. In the present work, our data demonstrated that BACH1 level was significantly increased in SAP patients, cellular, and animal models, while heat shock protein B1 (HSPB1) expression was weakened. Mechanistic assays validated that BACH1 acted as a transcriptional inhibitor of HSPB1. Moreover, HPDE6-C7 cells were stimulated with cerulein (Cer) and LPS to mimic the pathological stages of SAP in vitro. Depletion of BACH1 remarkably improved cell survival and alleviated the oxidative stress, ferroptosis, and inflammatory responses in SAP cell models. However, these changes were dramatically reversed upon co-inhibition of HSPB1. Animal findings confirmed that loss of BACH1 decreased pancreatic injury, inflammatory responses, and ferroptosis, but these effects were weakened by HSPB1 silence. Overall, these findings elucidate that the overexpression of BACH1 favors the ferroptosis and inflammation by transcriptionally inhibiting HSBP1, thereby exacerbating SAP progression.</p>\",\"PeriodicalId\":11291,\"journal\":{\"name\":\"Drug Development Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Drug Development Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ddr.22256\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drug Development Research","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ddr.22256","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0

摘要

重症急性胰腺炎(SAP)以胰腺急性炎症为特征。转录因子 BTB 和 CNC 同源物 1(BACH1)与多种生物过程有关,包括氧化应激、细胞凋亡和细胞周期调节。然而,其在 SAP 发病机制中的参与程度仍相对较低。在本研究中,我们的数据表明,在 SAP 患者、细胞和动物模型中,BACH1 水平显著升高,而热休克蛋白 B1(HSPB1)表达减弱。机理实验验证了 BACH1 是 HSPB1 的转录抑制剂。此外,HPDE6-C7细胞在体外受到cerulein(Cer)和LPS的刺激,以模拟SAP的病理阶段。在 SAP 细胞模型中,耗竭 BACH1 能显著提高细胞存活率,减轻氧化应激、铁蛋白沉着和炎症反应。然而,在同时抑制 HSPB1 后,这些变化被显著逆转。动物实验结果证实,BACH1 的缺失会减轻胰腺损伤、炎症反应和铁蛋白沉积,但这些作用会因 HSPB1 的沉默而减弱。总之,这些研究结果阐明了 BACH1 的过度表达会通过转录抑制 HSBP1 来促进铁蛋白沉积和炎症反应,从而加剧 SAP 的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
m6A-activated BACH1 exacerbates ferroptosis by epigenetic suppression HSPB1 in severe acute pancreatitis

Severe acute pancreatitis (SAP) is characterized by acute inflammation of the pancreas. The transcription factor BTB and CNC homology 1 (BACH1) has been implicated in various biological processes, including oxidative stress, apoptosis, and cell cycle regulation. However, its involvement in the pathogenesis of SAP remains relatively understudied. In the present work, our data demonstrated that BACH1 level was significantly increased in SAP patients, cellular, and animal models, while heat shock protein B1 (HSPB1) expression was weakened. Mechanistic assays validated that BACH1 acted as a transcriptional inhibitor of HSPB1. Moreover, HPDE6-C7 cells were stimulated with cerulein (Cer) and LPS to mimic the pathological stages of SAP in vitro. Depletion of BACH1 remarkably improved cell survival and alleviated the oxidative stress, ferroptosis, and inflammatory responses in SAP cell models. However, these changes were dramatically reversed upon co-inhibition of HSPB1. Animal findings confirmed that loss of BACH1 decreased pancreatic injury, inflammatory responses, and ferroptosis, but these effects were weakened by HSPB1 silence. Overall, these findings elucidate that the overexpression of BACH1 favors the ferroptosis and inflammation by transcriptionally inhibiting HSBP1, thereby exacerbating SAP progression.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
6.40
自引率
2.60%
发文量
104
审稿时长
6-12 weeks
期刊介绍: Drug Development Research focuses on research topics related to the discovery and development of new therapeutic entities. The journal publishes original research articles on medicinal chemistry, pharmacology, biotechnology and biopharmaceuticals, toxicology, and drug delivery, formulation, and pharmacokinetics. The journal welcomes manuscripts on new compounds and technologies in all areas focused on human therapeutics, as well as global management, health care policy, and regulatory issues involving the drug discovery and development process. In addition to full-length articles, Drug Development Research publishes Brief Reports on important and timely new research findings, as well as in-depth review articles. The journal also features periodic special thematic issues devoted to specific compound classes, new technologies, and broad aspects of drug discovery and development.
期刊最新文献
Targeted therapies for Glioblastoma multiforme (GBM): State-of-the-art and future prospects Knockdown of ENO1 promotes autophagy dependent-ferroptosis and suppresses glycolysis in breast cancer cells via the regulation of CST1. MLLT3 knockdown suppresses proliferation and cell mobility in human lung adenocarcinoma. PARP7i Clinical Candidate RBN-2397 Exerts Antiviral Activity by Modulating Interferon-β Associated Innate Immune Response in Macrophages. Agmatine: An Emerging Approach for Neuroprotection in Recurrent Ischemic Stroke Events in a Murine Model
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1