• 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

通过 TGF-β和 JNK 信号通路调控 p38α 对肿瘤血管生成和间质内皮转化的作用。

Regulation of tumor angiogenesis and mesenchymal-endothelial transition by p38α through TGF-β and JNK signaling.

机构信息

Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028, Barcelona, Spain.

ICREA, Pg. Lluís Companys 23, 08010, Barcelona, Spain.

出版信息

Nat Commun. 2019 Jul 11;10(1):3071. doi: 10.1038/s41467-019-10946-y.

DOI:10.1038/s41467-019-10946-y
PMID:31296856
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6624205/
Abstract

The formation of new blood vessels is essential for normal development, tissue repair and tumor growth. Here we show that inhibition of the kinase p38α enhances angiogenesis in human and mouse colon tumors. Mesenchymal cells can contribute to tumor angiogenesis by regulating proliferation and migration of endothelial cells. We show that p38α negatively regulates an angiogenic program in mesenchymal stem/stromal cells (MSCs), multipotent progenitors found in perivascular locations. This program includes the acquisition of an endothelial phenotype by MSCs mediated by both TGF-β and JNK, and negatively regulated by p38α. Abrogation of p38α in mesenchymal cells increases tumorigenesis, which correlates with enhanced angiogenesis. Using genetic models, we show that p38α regulates the acquisition of an endothelial-like phenotype by mesenchymal cells in colon tumors and damage tissue. Taken together, our results indicate that p38α in mesenchymal cells restrains a TGF-β-induced angiogenesis program including their ability to transdifferentiate into endothelial cells.

摘要

新血管的形成对于正常发育、组织修复和肿瘤生长至关重要。在这里，我们表明抑制激酶 p38α 可增强人和小鼠结肠肿瘤中的血管生成。间充质细胞可以通过调节内皮细胞的增殖和迁移来促进肿瘤血管生成。我们表明 p38α 负调控血管生成程序在间充质干细胞（MSC）中，多能祖细胞在血管周围位置发现。这个程序包括 MSC 通过 TGF-β和 JNK 介导的获得内皮表型，并且受到 p38α 的负调控。在间充质细胞中阻断 p38α 会增加肿瘤发生，这与增强的血管生成相关。使用遗传模型，我们表明 p38α 调节结肠肿瘤和损伤组织中间充质细胞获得类似内皮的表型。总之，我们的结果表明，间充质细胞中的 p38α 抑制 TGF-β诱导的血管生成程序，包括它们转分化为内皮细胞的能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/9e252238ad6a/41467_2019_10946_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/22789419eb20/41467_2019_10946_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/c6d8fc80dcf7/41467_2019_10946_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/9cf16fddbe8a/41467_2019_10946_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/38065cbdba0e/41467_2019_10946_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/a112f109f4be/41467_2019_10946_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/8e7c4eab8605/41467_2019_10946_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/363eba044ccb/41467_2019_10946_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/80ad2d3dfce9/41467_2019_10946_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/9e252238ad6a/41467_2019_10946_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/22789419eb20/41467_2019_10946_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/c6d8fc80dcf7/41467_2019_10946_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/9cf16fddbe8a/41467_2019_10946_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/38065cbdba0e/41467_2019_10946_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/a112f109f4be/41467_2019_10946_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/8e7c4eab8605/41467_2019_10946_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/363eba044ccb/41467_2019_10946_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/80ad2d3dfce9/41467_2019_10946_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d8f/6624205/9e252238ad6a/41467_2019_10946_Fig9_HTML.jpg

相似文献

1
Regulation of tumor angiogenesis and mesenchymal-endothelial transition by p38α through TGF-β and JNK signaling.通过 TGF-β和 JNK 信号通路调控 p38α 对肿瘤血管生成和间质内皮转化的作用。
Nat Commun. 2019 Jul 11;10(1):3071. doi: 10.1038/s41467-019-10946-y.
2
Transforming Growth Factor β/NR4A1-Inducible Breast Cancer Cell Migration and Epithelial-to-Mesenchymal Transition Is p38α (Mitogen-Activated Protein Kinase 14) Dependent.转化生长因子β/NR4A1诱导的乳腺癌细胞迁移和上皮-间质转化依赖于p38α（丝裂原活化蛋白激酶14）。
Mol Cell Biol. 2017 Aug 28;37(18). doi: 10.1128/MCB.00306-17. Print 2017 Sep 15.
3
Mesenchymal stem cells cancel azoxymethane-induced tumor initiation.间充质干细胞可消除氧化偶氮甲烷诱导的肿瘤起始。
Stem Cells. 2014 Apr;32(4):913-25. doi: 10.1002/stem.1594.
4
LY2228820 dimesylate, a selective inhibitor of p38 mitogen-activated protein kinase, reduces angiogenic endothelial cord formation in vitro and in vivo.LY2228820 二甲硫酸盐，一种 p38 丝裂原活化蛋白激酶的选择性抑制剂，可减少体外和体内的血管生成内皮索形成。
J Biol Chem. 2013 Mar 1;288(9):6743-53. doi: 10.1074/jbc.M112.425553. Epub 2013 Jan 18.
5
BMP-3 promotes mesenchymal stem cell proliferation through the TGF-beta/activin signaling pathway.骨形态发生蛋白-3 通过 TGF-β/激活素信号通路促进间充质干细胞增殖。
J Cell Physiol. 2010 Jun;223(3):658-66. doi: 10.1002/jcp.22064.
6
Dual function of p38α MAPK in colon cancer: suppression of colitis-associated tumor initiation but requirement for cancer cell survival.p38α MAPK 在结肠癌中的双重功能：抑制结肠炎相关肿瘤起始，但需要癌细胞存活。
Cancer Cell. 2014 Apr 14;25(4):484-500. doi: 10.1016/j.ccr.2014.02.019. Epub 2014 Mar 27.
7
Differential roles of JNK, ERK1/2, and p38 mitogen-activated protein kinases on endothelial cell tissue repair functions in response to tumor necrosis factor-α.JNK、ERK1/2和p38丝裂原活化蛋白激酶在肿瘤坏死因子-α刺激下对内皮细胞组织修复功能的不同作用
J Vasc Res. 2013;50(2):145-56. doi: 10.1159/000345525. Epub 2012 Dec 18.
8
Effect of TAK1 on osteogenic differentiation of mesenchymal stem cells by regulating BMP-2 via Wnt/β-catenin and MAPK pathway.TAK1通过Wnt/β-连环蛋白和丝裂原活化蛋白激酶（MAPK）途径调节骨形态发生蛋白-2（BMP-2）对间充质干细胞成骨分化的影响。
Organogenesis. 2018 Jan 2;14(1):36-45. doi: 10.1080/15476278.2018.1455010.
9
IL-6 and TGF-α costimulate mesenchymal stem cell vascular endothelial growth factor production by ERK-, JNK-, and PI3K-mediated mechanisms.白细胞介素-6 和转化生长因子-α通过 ERK、JNK 和 PI3K 介导的机制共同刺激间充质干细胞血管内皮生长因子的产生。
Shock. 2011 May;35(5):512-6. doi: 10.1097/SHK.0b013e31820b2fb9.
10
Mammalian target of rapamycin pathway promotes tumor-induced angiogenesis in adenoid cystic carcinoma: its suppression by isoliquiritigenin through dual activation of c-Jun NH2-terminal kinase and inhibition of extracellular signal-regulated kinase.雷帕霉素靶蛋白通路促进腺样囊性癌中的肿瘤诱导血管生成：异甘草素通过双重激活 c-Jun NH2-末端激酶和抑制细胞外信号调节激酶来抑制它。
J Pharmacol Exp Ther. 2010 Aug;334(2):500-12. doi: 10.1124/jpet.110.167692. Epub 2010 May 18.

引用本文的文献

1
Loss of Zonula Occludens-1 (ZO-1) Enhances Angiogenic Signaling in Ovarian Cancer Cells.闭合蛋白1（ZO-1）缺失增强卵巢癌细胞中的血管生成信号。
Int J Mol Sci. 2025 Aug 29;26(17):8389. doi: 10.3390/ijms26178389.
2
Development and validation of a novel risk stratification signature derived from migrasome and tumor microenvironment-related genes for molecular subtyping and improving clinical outcomes in head and neck squamous cell carcinoma.基于迁移小体和肿瘤微环境相关基因的新型风险分层特征的开发与验证，用于头颈部鳞状细胞癌的分子分型及改善临床结局
Ann Med. 2025 Dec;57(1):2558121. doi: 10.1080/07853890.2025.2558121. Epub 2025 Sep 9.
3

本文引用的文献

1
Mouse Genome Database (MGD)-2018: knowledgebase for the laboratory mouse.小鼠基因组数据库（MGD）-2018：实验小鼠知识库。
Nucleic Acids Res. 2018 Jan 4;46(D1):D836-D842. doi: 10.1093/nar/gkx1006.
2
Preexisting endothelial cells mediate cardiac neovascularization after injury.损伤后，预先存在的内皮细胞介导心脏新生血管形成。
J Clin Invest. 2017 Aug 1;127(8):2968-2981. doi: 10.1172/JCI93868. Epub 2017 Jun 26.
3
Pericytes of Multiple Organs Do Not Behave as Mesenchymal Stem Cells In Vivo.多器官的周细胞在体内并非表现为间充质干细胞。
Lithium-doped calcium silicate scaffolds-activated M2-polarized macrophage-derived miR-145-5p-riched extracellular vesicles to enhance osteoimmunomodulation for accelerating bone regeneration.
锂掺杂硅酸钙支架激活M2极化巨噬细胞衍生的富含miR-145-5p的细胞外囊泡，以增强骨免疫调节作用，加速骨再生。
J Nanobiotechnology. 2025 Aug 25;23(1):586. doi: 10.1186/s12951-025-03679-2.
4
Extruded nanovesicles derived from umbilical cord mesenchymal stem cells exhibit No tumorigenic potential.源自脐带间充质干细胞的挤出纳米囊泡无致瘤潜力。
Bioact Mater. 2025 Jul 3;52:866-876. doi: 10.1016/j.bioactmat.2025.06.056. eCollection 2025 Oct.
5
Tumor-associated mesenchymal stem/stromal cells in tumor microenvironment and carcinogenesis.肿瘤微环境中的肿瘤相关间充质干细胞与肿瘤发生
Exp Hematol Oncol. 2025 Jul 17;14(1):97. doi: 10.1186/s40164-025-00688-7.
6
TGF-β3 promotes vascular normalization of prostate cancer to potentiate immunotherapy and chemotherapy.转化生长因子-β3促进前列腺癌血管正常化以增强免疫治疗和化疗效果。
Cancer Immunol Immunother. 2025 Jul 12;74(8):268. doi: 10.1007/s00262-025-04103-2.
7
LncRNAs in hypoxic microenvironment; insight in their impact in cancer biology.缺氧微环境中的长链非编码RNA；对其在癌症生物学中影响的见解
Funct Integr Genomics. 2025 Jul 2;25(1):142. doi: 10.1007/s10142-025-01635-9.
8
Understanding chronic inflammation: couplings between cytokines, ROS, NO, Ca , HIF-1α, Nrf2 and autophagy.理解慢性炎症：细胞因子、活性氧、一氧化氮、钙离子、低氧诱导因子-1α、核因子E2相关因子2与自噬之间的相互关系
Front Immunol. 2025 Apr 8;16:1558263. doi: 10.3389/fimmu.2025.1558263. eCollection 2025.
9
β-blocker suppresses both tumoral sympathetic neurons and perivascular macrophages during oncolytic herpes virotherapy.在溶瘤性疱疹病毒疗法期间，β受体阻滞剂可抑制肿瘤交感神经元和血管周围巨噬细胞。
J Immunother Cancer. 2025 Apr 5;13(4):e011322. doi: 10.1136/jitc-2024-011322.
10
Cancer-secreted exosomal miR-1825 induces angiogenesis to promote colorectal cancer metastasis.癌症分泌的外泌体miR-1825诱导血管生成以促进结直肠癌转移。
Cancer Cell Int. 2025 Feb 22;25(1):63. doi: 10.1186/s12935-025-03674-5.
Cell Stem Cell. 2017 Mar 2;20(3):345-359.e5. doi: 10.1016/j.stem.2016.12.006. Epub 2017 Jan 19.
4
Endothelial cells are progenitors of cardiac pericytes and vascular smooth muscle cells.内皮细胞是心脏周细胞和血管平滑肌细胞的前体细胞。
Nat Commun. 2016 Aug 12;7:12422. doi: 10.1038/ncomms12422.
5
Clinical development of galunisertib (LY2157299 monohydrate), a small molecule inhibitor of transforming growth factor-beta signaling pathway.转化生长因子-β信号通路小分子抑制剂加鲁尼西替（LY2157299一水合物）的临床开发
Drug Des Devel Ther. 2015 Aug 10;9:4479-99. doi: 10.2147/DDDT.S86621. eCollection 2015.
6
Pharmacological inhibition of p38 MAPK reduces tumor growth in patient-derived xenografts from colon tumors.对p38丝裂原活化蛋白激酶的药理学抑制可减少来自结肠肿瘤的患者来源异种移植瘤中的肿瘤生长。
Oncotarget. 2015 Apr 20;6(11):8539-51. doi: 10.18632/oncotarget.3816.
7
Vascular wall progenitor cells in health and disease.血管壁祖细胞在健康与疾病中的作用。
Circ Res. 2015 Apr 10;116(8):1392-412. doi: 10.1161/CIRCRESAHA.116.305368.
8
Stromal gene expression defines poor-prognosis subtypes in colorectal cancer.基质基因表达定义了结直肠癌的预后不良亚型。
Nat Genet. 2015 Apr;47(4):320-9. doi: 10.1038/ng.3225. Epub 2015 Feb 23.
9
limma powers differential expression analyses for RNA-sequencing and microarray studies.limma为RNA测序和微阵列研究提供差异表达分析的动力。
Nucleic Acids Res. 2015 Apr 20;43(7):e47. doi: 10.1093/nar/gkv007. Epub 2015 Jan 20.
10
Perivascular Gli1+ progenitors are key contributors to injury-induced organ fibrosis.血管周围Gli1+祖细胞是损伤诱导器官纤维化的关键促成因素。
Cell Stem Cell. 2015 Jan 8;16(1):51-66. doi: 10.1016/j.stem.2014.11.004. Epub 2014 Nov 20.