• 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

SETDB1 调节杜氏肌营养不良症肌管中的 TGFβ 反应。

SETDB1 modulates the TGFβ response in Duchenne muscular dystrophy myotubes.

机构信息

Université Paris Cité, CNRS, Epigenetics and Cell Fate, UMR7216, F-75013 Paris, France.

Sorbonne Université, Inserm, Institut de Myologie, Centre de Recherche en Myologie, Paris, France.

出版信息

Sci Adv. 2024 May 3;10(18):eadj8042. doi: 10.1126/sciadv.adj8042. Epub 2024 May 1.

DOI:10.1126/sciadv.adj8042
PMID:38691608
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11062573/
Abstract

Overactivation of the transforming growth factor-β (TGFβ) signaling in Duchenne muscular dystrophy (DMD) is a major hallmark of disease progression, leading to fibrosis and muscle dysfunction. Here, we investigated the role of SETDB1 (SET domain, bifurcated 1), a histone lysine methyltransferase involved in muscle differentiation. Our data show that, following TGFβ induction, SETDB1 accumulates in the nuclei of healthy myotubes while being already present in the nuclei of DMD myotubes where TGFβ signaling is constitutively activated. Transcriptomics revealed that depletion of SETDB1 in DMD myotubes leads to down-regulation of TGFβ target genes coding for secreted factors involved in extracellular matrix remodeling and inflammation. Consequently, SETDB1 silencing in DMD myotubes abrogates the deleterious effect of their secretome on myoblast differentiation by impairing myoblast pro-fibrotic response. Our findings indicate that SETDB1 potentiates the TGFβ-driven fibrotic response in DMD muscles, providing an additional axis for therapeutic intervention.

摘要

转化生长因子-β（TGFβ）信号在杜氏肌营养不良症（DMD）中的过度激活是疾病进展的主要标志，导致纤维化和肌肉功能障碍。在这里，我们研究了 SETDB1（SET 结构域，分叉 1）的作用，它是一种参与肌肉分化的组蛋白赖氨酸甲基转移酶。我们的数据表明，在 TGFβ 诱导后，SETDB1 在健康肌管的核内积累，而在 TGFβ 信号持续激活的 DMD 肌管的核内已经存在。转录组学显示，在 DMD 肌管中敲低 SETDB1 导致编码参与细胞外基质重塑和炎症的分泌因子的 TGFβ 靶基因下调。因此，DMD 肌管中 SETDB1 的沉默通过损害成肌细胞的促纤维化反应来消除其分泌组对成肌细胞分化的有害影响。我们的研究结果表明，SETDB1 增强了 DMD 肌肉中 TGFβ 驱动的纤维化反应，为治疗干预提供了另一个靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3af9/11062573/97e94037f87e/sciadv.adj8042-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3af9/11062573/94ed03fd35be/sciadv.adj8042-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3af9/11062573/258c74bec272/sciadv.adj8042-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3af9/11062573/925e26670993/sciadv.adj8042-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3af9/11062573/72f485565dcd/sciadv.adj8042-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3af9/11062573/97e94037f87e/sciadv.adj8042-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3af9/11062573/94ed03fd35be/sciadv.adj8042-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3af9/11062573/258c74bec272/sciadv.adj8042-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3af9/11062573/925e26670993/sciadv.adj8042-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3af9/11062573/72f485565dcd/sciadv.adj8042-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3af9/11062573/97e94037f87e/sciadv.adj8042-f5.jpg

相似文献

1
SETDB1 modulates the TGFβ response in Duchenne muscular dystrophy myotubes.SETDB1 调节杜氏肌营养不良症肌管中的 TGFβ 反应。
Sci Adv. 2024 May 3;10(18):eadj8042. doi: 10.1126/sciadv.adj8042. Epub 2024 May 1.
2
Acute conversion of patient-derived Duchenne muscular dystrophy iPSC into myotubes reveals constitutive and inducible over-activation of TGFβ-dependent pro-fibrotic signaling.患者来源的杜氏肌营养不良诱导多能干细胞向肌管的急性转化揭示了TGFβ依赖性促纤维化信号的组成性和诱导性过度激活。
Skelet Muscle. 2020 May 2;10(1):13. doi: 10.1186/s13395-020-00224-7.
3
ADAMTS-5 inhibition reduces muscle inflammation and fibrosis and improves function in mouse models of Duchenne muscular dystrophy.ADAMTS-5抑制可减轻杜氏肌营养不良小鼠模型中的肌肉炎症和纤维化，并改善其功能。
Sci Transl Med. 2025 Jun 18;17(803):eado2112. doi: 10.1126/scitranslmed.ado2112.
4
Skeletal Ryanodine Receptors Are Involved in Impaired Myogenic Differentiation in Duchenne Muscular Dystrophy Patients.骨架型兰尼碱受体参与杜氏肌营养不良症患者的肌原性分化受损。
Int J Mol Sci. 2021 Nov 30;22(23):12985. doi: 10.3390/ijms222312985.
5
Transforming growth factor type-β inhibits Mas receptor expression in fibroblasts but not in myoblasts or differentiated myotubes; Relevance to fibrosis associated to muscular dystrophies.转化生长因子-β抑制成纤维细胞中 Mas 受体的表达，但不抑制成肌细胞或分化的肌管中 Mas 受体的表达；与肌肉疾病相关的纤维化的相关性。
Biofactors. 2015 Mar-Apr;41(2):111-20. doi: 10.1002/biof.1208. Epub 2015 Mar 23.
6
Skeletal muscle secretome in Duchenne muscular dystrophy: a pivotal anti-inflammatory role of adiponectin.杜兴氏肌肉营养不良症中的骨骼肌分泌组：脂联素的关键抗炎作用。
Cell Mol Life Sci. 2017 Jul;74(13):2487-2501. doi: 10.1007/s00018-017-2465-5. Epub 2017 Feb 10.
7
Skeletal Muscle Differentiation on a Chip Shows Human Donor Mesoangioblasts' Efficiency in Restoring Dystrophin in a Duchenne Muscular Dystrophy Model.芯片上的骨骼肌分化显示人供体中血管周细胞在杜兴氏肌营养不良模型中恢复抗肌萎缩蛋白的效率。
Stem Cells Transl Med. 2016 Dec;5(12):1676-1683. doi: 10.5966/sctm.2015-0053. Epub 2016 Aug 8.
8
Sertoli Cells Improve Myogenic Differentiation, Reduce Fibrogenic Markers, and Induce Utrophin Expression in Human DMD Myoblasts.支持细胞促进肌生成分化，减少成纤维标志物，并诱导人类 DMD 成肌细胞表达肌联蛋白。
Biomolecules. 2021 Oct 12;11(10):1504. doi: 10.3390/biom11101504.
9
Obligatory and accessory respiratory muscle structure, function and control in early and advanced disease in the mdx mouse model of Duchenne muscular dystrophy.杜兴氏肌肉营养不良症mdx小鼠模型中早期和晚期疾病阶段的呼吸主肌与辅助肌的结构、功能及调控
J Physiol. 2025 Jun 18. doi: 10.1113/JP288709.
10
The FibromiR miR-214-3p Is Upregulated in Duchenne Muscular Dystrophy and Promotes Differentiation of Human Fibro-Adipogenic Muscle Progenitors.纤维肌微 RNA miR-214-3p 在杜氏肌营养不良症中上调，并促进人成纤维脂肪肌祖细胞的分化。
Cells. 2021 Jul 20;10(7):1832. doi: 10.3390/cells10071832.

引用本文的文献

1
The SUV39 Family of H3K9 Methyltransferases in Skeletal Muscle Stem Cells.骨骼肌干细胞中H3K9甲基转移酶的SUV39家族
FASEB Bioadv. 2025 May 3;7(6):e70014. doi: 10.1096/fba.2024-00102. eCollection 2025 Jun.

本文引用的文献

1
SETDB1: A perspective into immune cell function and cancer immunotherapy.SETDB1：免疫细胞功能与癌症免疫治疗的新视角
Immunology. 2023 May;169(1):3-12. doi: 10.1111/imm.13619. Epub 2022 Dec 21.
2
Establishment of H3K9-methylated heterochromatin and its functions in tissue differentiation and maintenance.建立 H3K9 甲基化异染色质及其在组织分化和维持中的功能。
Nat Rev Mol Cell Biol. 2022 Sep;23(9):623-640. doi: 10.1038/s41580-022-00483-w. Epub 2022 May 13.
3
SETDB1 fuels the lung cancer phenotype by modulating epigenome, 3D genome organization and chromatin mechanical properties.
SETDB1通过调节表观基因组、三维基因组组织和染色质机械特性来促进肺癌表型。
Nucleic Acids Res. 2022 May 6;50(8):4389-4413. doi: 10.1093/nar/gkac234.
4
Lack of and synergistically stimulates myofibre hypertrophy and accelerates muscle regeneration.缺乏 和 协同刺激肌纤维肥大，并加速肌肉再生。
Elife. 2022 Mar 24;11:e77610. doi: 10.7554/eLife.77610.
5
Histone methyltransferase SETDB1 inhibits TGF-β-induced epithelial-mesenchymal transition in pulmonary fibrosis by regulating SNAI1 expression and the ferroptosis signaling pathway.组蛋白甲基转移酶SETDB1通过调节SNAI1表达和铁死亡信号通路抑制转化生长因子-β诱导的肺纤维化上皮-间质转化。
Arch Biochem Biophys. 2022 Jan 15;715:109087. doi: 10.1016/j.abb.2021.109087. Epub 2021 Nov 18.
6
clusterProfiler 4.0: A universal enrichment tool for interpreting omics data.clusterProfiler 4.0：用于解释组学数据的通用富集工具。
Innovation (Camb). 2021 Jul 1;2(3):100141. doi: 10.1016/j.xinn.2021.100141. eCollection 2021 Aug 28.
7
Structure, Activity and Function of the SETDB1 Protein Methyltransferase.SETDB1蛋白甲基转移酶的结构、活性与功能
Life (Basel). 2021 Aug 11;11(8):817. doi: 10.3390/life11080817.
8
TGFβ signaling curbs cell fusion and muscle regeneration.TGFβ 信号通路抑制细胞融合和肌肉再生。
Nat Commun. 2021 Feb 2;12(1):750. doi: 10.1038/s41467-020-20289-8.
9
Histone Methyltransferase SETDB1: A Common Denominator of Tumorigenesis with Therapeutic Potential.组蛋白甲基转移酶 SETDB1：具有治疗潜力的肿瘤发生的共同特征。
Cancer Res. 2021 Feb 1;81(3):525-534. doi: 10.1158/0008-5472.CAN-20-2906. Epub 2020 Oct 28.
10
The discovery of dystrophin, the protein product of the Duchenne muscular dystrophy gene.肌营养不良蛋白的发现，该蛋白是杜氏肌营养不良症基因的产物。
FEBS J. 2020 Sep;287(18):3879-3887. doi: 10.1111/febs.15466. Epub 2020 Jul 21.