• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

IRE1α/XBP1 信号轴驱动成年骨骼肌中的成肌细胞融合。

The IRE1α/XBP1 signaling axis drives myoblast fusion in adult skeletal muscle.

机构信息

Department of Pharmacological and Pharmaceutical Sciences, University of Houston College of Pharmacy, Houston, TX, 77204, USA.

Department of Biology and Biochemistry, University of Houston, Houston, TX, 77204, USA.

出版信息

EMBO Rep. 2024 Aug;25(8):3627-3650. doi: 10.1038/s44319-024-00197-4. Epub 2024 Jul 9.

DOI:10.1038/s44319-024-00197-4
PMID:38982191
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11316051/
Abstract

Skeletal muscle regeneration involves a signaling network that regulates the proliferation, differentiation, and fusion of muscle precursor cells to injured myofibers. IRE1α, one of the arms of the unfolded protein response, regulates cellular proteostasis in response to ER stress. Here, we demonstrate that inducible deletion of IRE1α in satellite cells of mice impairs skeletal muscle regeneration through inhibiting myoblast fusion. Knockdown of IRE1α or its downstream target, X-box protein 1 (XBP1), also inhibits myoblast fusion during myogenesis. Transcriptome analysis revealed that knockdown of IRE1α or XBP1 dysregulates the gene expression of molecules involved in myoblast fusion. The IRE1α-XBP1 axis mediates the gene expression of multiple profusion molecules, including myomaker (Mymk). Spliced XBP1 (sXBP1) transcription factor binds to the promoter of Mymk gene during myogenesis. Overexpression of myomaker in IRE1α-knockdown cultures rescues fusion defects. Inducible deletion of IRE1α in satellite cells also inhibits myoblast fusion and myofiber hypertrophy in response to functional overload. Collectively, our study demonstrates that IRE1α promotes myoblast fusion through sXBP1-mediated up-regulation of the gene expression of multiple profusion molecules, including myomaker.

摘要

骨骼肌再生涉及一个信号网络，该网络调节肌肉前体细胞的增殖、分化和融合，以修复受损的肌纤维。IRE1α 是未折叠蛋白反应的一个分支，可调节细胞内蛋白质稳态，以响应内质网应激。在这里，我们证明了在小鼠卫星细胞中诱导性敲除 IRE1α 会通过抑制成肌细胞融合而损害骨骼肌再生。IRE1α 或其下游靶点 X 盒蛋白 1（XBP1）的敲低也会在肌发生过程中抑制成肌细胞融合。转录组分析显示，敲低 IRE1α 或 XBP1 会使参与成肌细胞融合的分子的基因表达失调。IRE1α-XBP1 轴介导多个促融合分子的基因表达，包括肌生成素（Mymk）。剪接的 XBP1（sXBP1）转录因子在肌发生过程中结合到 Mymk 基因的启动子上。在 IRE1α 敲低培养物中转基因过表达肌生成素可挽救融合缺陷。在卫星细胞中诱导性敲除 IRE1α 也会抑制成肌细胞融合和肌纤维肥大对功能过载的反应。总之，我们的研究表明，IRE1α 通过 sXBP1 介导的多个促融合分子（包括肌生成素）的基因表达上调来促进成肌细胞融合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/8a613e8754a4/44319_2024_197_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/676fccf79a2c/44319_2024_197_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/b584f878d080/44319_2024_197_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/ac18e0da8f4f/44319_2024_197_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/8f0af1d9d65a/44319_2024_197_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/983b17964502/44319_2024_197_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/4e7d33ce78c8/44319_2024_197_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/db01d5ce7ade/44319_2024_197_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/d2c18bc16a31/44319_2024_197_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/d5982c08d7de/44319_2024_197_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/ec1a71cc58dc/44319_2024_197_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/3902e63698ac/44319_2024_197_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/201a8f079a50/44319_2024_197_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/8a613e8754a4/44319_2024_197_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/676fccf79a2c/44319_2024_197_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/b584f878d080/44319_2024_197_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/ac18e0da8f4f/44319_2024_197_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/8f0af1d9d65a/44319_2024_197_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/983b17964502/44319_2024_197_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/4e7d33ce78c8/44319_2024_197_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/db01d5ce7ade/44319_2024_197_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/d2c18bc16a31/44319_2024_197_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/d5982c08d7de/44319_2024_197_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/ec1a71cc58dc/44319_2024_197_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/3902e63698ac/44319_2024_197_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/201a8f079a50/44319_2024_197_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a4b/11316051/8a613e8754a4/44319_2024_197_Fig13_ESM.jpg

相似文献

1
The IRE1α/XBP1 signaling axis drives myoblast fusion in adult skeletal muscle.IRE1α/XBP1 信号轴驱动成年骨骼肌中的成肌细胞融合。
EMBO Rep. 2024 Aug;25(8):3627-3650. doi: 10.1038/s44319-024-00197-4. Epub 2024 Jul 9.
2
The IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism.IRE1/XBP1 信号轴通过非细胞自主机制促进骨骼肌再生。
Elife. 2021 Nov 23;10:e73215. doi: 10.7554/eLife.73215.
3
Genetic Mutations in jamb, jamc, and myomaker Revealed Different Roles on Myoblast Fusion and Muscle Growth.jamb、jamc 和 myomaker 中的基因突变揭示了它们在成肌细胞融合和肌肉生长中的不同作用。
Mar Biotechnol (NY). 2019 Feb;21(1):111-123. doi: 10.1007/s10126-018-9865-x. Epub 2018 Nov 22.
4
IRE1-XBP1 Pathway of the Unfolded Protein Response Is Required during Early Differentiation of C2C12 Myoblasts.未折叠蛋白反应的 IRE1-XBP1 途径在 C2C12 成肌细胞的早期分化过程中是必需的。
Int J Mol Sci. 2019 Dec 26;21(1):182. doi: 10.3390/ijms21010182.
5
Selenoprotein S protects against adipocyte death through mediation of the IRE1α-sXBP1 pathway.硒蛋白 S 通过介导 IRE1α-sXBP1 通路来防止脂肪细胞死亡。
Biochem Biophys Res Commun. 2018 Sep 18;503(4):2866-2871. doi: 10.1016/j.bbrc.2018.08.057. Epub 2018 Aug 24.
6
Common and Distinctive Functions of the Hippo Effectors Taz and Yap in Skeletal Muscle Stem Cell Function.河马效应因子Taz和Yap在骨骼肌干细胞功能中的共同和独特作用。
Stem Cells. 2017 Aug;35(8):1958-1972. doi: 10.1002/stem.2652. Epub 2017 Jun 27.
7
IRE1α-XBP1 signaling in leukocytes controls prostaglandin biosynthesis and pain.IRE1α-XBP1 信号通路在白细胞中控制前列腺素生物合成和痛觉。
Science. 2019 Jul 19;365(6450). doi: 10.1126/science.aau6499.
8
MyD88 promotes myoblast fusion in a cell-autonomous manner.MyD88 以细胞自主的方式促进成肌细胞融合。
Nat Commun. 2017 Nov 20;8(1):1624. doi: 10.1038/s41467-017-01866-w.
9
Fusogenic micropeptide Myomixer is essential for satellite cell fusion and muscle regeneration.融合性微小肽 Myomixer 对于卫星细胞融合和肌肉再生是必不可少的。
Proc Natl Acad Sci U S A. 2018 Apr 10;115(15):3864-3869. doi: 10.1073/pnas.1800052115. Epub 2018 Mar 26.
10
IRE1α-XBP1 pathway promotes melanoma progression by regulating IL-6/STAT3 signaling.IRE1α-XBP1通路通过调节IL-6/STAT3信号促进黑色素瘤进展。
J Transl Med. 2017 Feb 21;15(1):42. doi: 10.1186/s12967-017-1147-2.

引用本文的文献

1
The canonical ER stress IRE1α/XBP1 pathway mediates skeletal muscle wasting during pancreatic cancer cachexia.经典的内质网应激IRE1α/XBP1信号通路介导胰腺癌恶病质期间的骨骼肌萎缩。
bioRxiv. 2025 Aug 4:2025.05.05.652304. doi: 10.1101/2025.05.05.652304.
2
RyR1 Is Involved in the Control of Myogenesis.兰尼碱受体1参与肌发生的调控。
Cells. 2025 Jan 21;14(3):158. doi: 10.3390/cells14030158.
3
A stress paradox: the dual role of the unfolded protein response in the placenta.一种应激悖论：未折叠蛋白反应在胎盘中的双重作用。

本文引用的文献

1
Make Interactive Complex Heatmaps in R.在 R 中制作交互式复杂热图。
Bioinformatics. 2022 Feb 7;38(5):1460-1462. doi: 10.1093/bioinformatics/btab806.
2
The IRE1/XBP1 signaling axis promotes skeletal muscle regeneration through a cell non-autonomous mechanism.IRE1/XBP1 信号轴通过非细胞自主机制促进骨骼肌再生。
Elife. 2021 Nov 23;10:e73215. doi: 10.7554/eLife.73215.
3
ReMap 2022: a database of Human, Mouse, Drosophila and Arabidopsis regulatory regions from an integrative analysis of DNA-binding sequencing experiments.
Front Endocrinol (Lausanne). 2024 Dec 20;15:1525189. doi: 10.3389/fendo.2024.1525189. eCollection 2024.
4
Single-nucleus transcriptomic analysis reveals the regulatory circuitry of myofiber XBP1 during regenerative myogenesis.单核转录组分析揭示了再生性肌生成过程中肌纤维XBP1的调控回路。
iScience. 2024 Nov 12;27(12):111372. doi: 10.1016/j.isci.2024.111372. eCollection 2024 Dec 20.
ReMap 2022：一个整合了 DNA 结合测序实验分析的人类、小鼠、果蝇和拟南芥调控区域数据库。
Nucleic Acids Res. 2022 Jan 7;50(D1):D316-D325. doi: 10.1093/nar/gkab996.
4
All for One and One for All: Regenerating Skeletal Muscle.众志成城：修复骨骼肌。
Cold Spring Harb Perspect Biol. 2022 Aug 1;14(8):a040824. doi: 10.1101/cshperspect.a040824.
5
Targeting the IRE1α/XBP1s pathway suppresses CARM1-expressing ovarian cancer.靶向 IRE1α/XBP1s 通路抑制表达 CARM1 的卵巢癌。
Nat Commun. 2021 Sep 7;12(1):5321. doi: 10.1038/s41467-021-25684-3.
6
Roles of XBP1s in Transcriptional Regulation of Target Genes.XBP1s在靶基因转录调控中的作用。
Biomedicines. 2021 Jul 8;9(7):791. doi: 10.3390/biomedicines9070791.
7
IRE1α regulates skeletal muscle regeneration through Myostatin mRNA decay.肌醇需求酶1α（IRE1α）通过肌肉生长抑制素（Myostatin）信使核糖核酸（mRNA）降解来调节骨骼肌再生。
J Clin Invest. 2021 Jul 20;131(17). doi: 10.1172/JCI143737.
8
PERK Signaling Controls Myoblast Differentiation by Regulating MicroRNA Networks.PERK信号通路通过调控微小RNA网络来控制成肌细胞分化。
Front Cell Dev Biol. 2021 May 28;9:670435. doi: 10.3389/fcell.2021.670435. eCollection 2021.
9
Perspectives on skeletal muscle stem cells.骨骼肌干细胞的研究进展。
Nat Commun. 2021 Jan 29;12(1):692. doi: 10.1038/s41467-020-20760-6.
10
Human myotube formation is determined by MyoD-Myomixer/Myomaker axis.人类肌管的形成由MyoD-Myomixer/Myomaker轴决定。
Sci Adv. 2020 Dec 18;6(51). doi: 10.1126/sciadv.abc4062. Print 2020 Dec.