• 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

Cavin-1/窖蛋白-1 相互作用通过干扰 BMPR2/窖蛋白-1 结合来减弱肺动脉高压中的 BMP/Smad 信号传导。

The Cavin-1/Caveolin-1 interaction attenuates BMP/Smad signaling in pulmonary hypertension by interfering with BMPR2/Caveolin-1 binding.

机构信息

Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.

Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, 602-8566, Japan.

出版信息

Commun Biol. 2024 Jan 5;7(1):40. doi: 10.1038/s42003-023-05693-2.

DOI:10.1038/s42003-023-05693-2
PMID:38182755
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10770141/
Abstract

Caveolin-1 (CAV1) and Cavin-1 are components of caveolae, both of which interact with and influence the composition and stabilization of caveolae. CAV1 is associated with pulmonary arterial hypertension (PAH). Bone morphogenetic protein (BMP) type 2 receptor (BMPR2) is localized in caveolae associated with CAV1 and is commonly mutated in PAH. Here, we show that BMP/Smad signaling is suppressed in pulmonary microvascular endothelial cells of CAV1 knockout mice. Moreover, hypoxia enhances the CAV1/Cavin-1 interaction but attenuates the CAV1/BMPR2 interaction and BMPR2 membrane localization in pulmonary artery endothelial cells (PAECs). Both Cavin-1 and BMPR2 are associated with the CAV1 scaffolding domain. Cavin-1 decreases BMPR2 membrane localization by inhibiting the interaction of BMPR2 with CAV1 and reduces Smad signal transduction in PAECs. Furthermore, Cavin-1 knockdown is resistant to CAV1-induced pulmonary hypertension in vivo. We demonstrate that the Cavin-1/Caveolin-1 interaction attenuates BMP/Smad signaling and is a promising target for the treatment of PAH.

摘要

窖蛋白-1（CAV1）和窖蛋白-1 相关蛋白-1（Cavin-1）是质膜凹陷（ caveolae ）的组成部分，两者相互作用并影响质膜凹陷的组成和稳定。CAV1 与肺动脉高压（PAH）有关。骨形态发生蛋白（BMP）型 2 受体（BMPR2）定位于与 CAV1 相关的质膜凹陷中，在 PAH 中常见突变。在这里，我们表明 CAV1 敲除小鼠的肺微血管内皮细胞中的 BMP/Smad 信号受到抑制。此外，低氧增强 CAV1/Cavin-1 相互作用，但减弱 CAV1/BMPR2 相互作用和 BMPR2 在肺动脉内皮细胞（PAECs）中的膜定位。Cavin-1 和 BMPR2 都与 CAV1 支架结构域相关。Cavin-1 通过抑制 BMPR2 与 CAV1 的相互作用来减少 BMPR2 的膜定位，并减少 PAECs 中的 Smad 信号转导。此外，Cavin-1 敲低可抵抗体内 CAV1 诱导的肺动脉高压。我们证明 Cavin-1/Caveolin-1 相互作用减弱了 BMP/Smad 信号，是治疗 PAH 的有前途的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fa/10770141/5f7a988e5254/42003_2023_5693_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fa/10770141/970cc83ce50b/42003_2023_5693_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fa/10770141/a8812e9dfaf4/42003_2023_5693_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fa/10770141/0a027ce1c558/42003_2023_5693_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fa/10770141/ba371c3ebaf1/42003_2023_5693_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fa/10770141/16221bbf0f7c/42003_2023_5693_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fa/10770141/c7beaeb0bef9/42003_2023_5693_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fa/10770141/5f7a988e5254/42003_2023_5693_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fa/10770141/970cc83ce50b/42003_2023_5693_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fa/10770141/a8812e9dfaf4/42003_2023_5693_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fa/10770141/0a027ce1c558/42003_2023_5693_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fa/10770141/ba371c3ebaf1/42003_2023_5693_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fa/10770141/16221bbf0f7c/42003_2023_5693_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fa/10770141/c7beaeb0bef9/42003_2023_5693_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fa/10770141/5f7a988e5254/42003_2023_5693_Fig7_HTML.jpg

相似文献

1
The Cavin-1/Caveolin-1 interaction attenuates BMP/Smad signaling in pulmonary hypertension by interfering with BMPR2/Caveolin-1 binding.Cavin-1/窖蛋白-1 相互作用通过干扰 BMPR2/窖蛋白-1 结合来减弱肺动脉高压中的 BMP/Smad 信号传导。
Commun Biol. 2024 Jan 5;7(1):40. doi: 10.1038/s42003-023-05693-2.
2
CCL5 deficiency rescues pulmonary vascular dysfunction, and reverses pulmonary hypertension via caveolin-1-dependent BMPR2 activation.CCL5 缺乏通过 caveolin-1 依赖性 BMPR2 激活挽救肺血管功能障碍和逆转肺动脉高压。
J Mol Cell Cardiol. 2018 Mar;116:41-56. doi: 10.1016/j.yjmcc.2018.01.016. Epub 2018 Jan 31.
3
Type I interferon activation and endothelial dysfunction in caveolin-1 insufficiency-associated pulmonary arterial hypertension. caveolin-1 不足相关肺动脉高压中 I 型干扰素的激活和血管内皮功能障碍。
Proc Natl Acad Sci U S A. 2021 Mar 16;118(11). doi: 10.1073/pnas.2010206118.
4
Endocytic crosstalk: cavins, caveolins, and caveolae regulate clathrin-independent endocytosis.内吞作用的相互作用：窖蛋白、小窝蛋白和小窝调控网格蛋白非依赖性内吞作用。
PLoS Biol. 2014 Apr 8;12(4):e1001832. doi: 10.1371/journal.pbio.1001832. eCollection 2014 Apr.
5
Deformation of caveolae impacts global transcription and translation processes through relocalization of cavin-1.通过 cavin-1 的重定位，质膜微囊的变形会影响全局转录和翻译过程。
J Biol Chem. 2022 Jun;298(6):102005. doi: 10.1016/j.jbc.2022.102005. Epub 2022 May 2.
6
Differential impact of caveolae and caveolin-1 scaffolds on the membrane raft proteome.网格蛋白小窝及其相关蛋白 1 支架对膜筏蛋白组的差异影响。
Mol Cell Proteomics. 2011 Oct;10(10):M110.007146. doi: 10.1074/mcp.M110.007146. Epub 2011 Jul 13.
7
Elafin Reverses Pulmonary Hypertension via Caveolin-1-Dependent Bone Morphogenetic Protein Signaling.弹性蛋白通过小窝蛋白-1依赖的骨形态发生蛋白信号通路逆转肺动脉高压。
Am J Respir Crit Care Med. 2015 Jun 1;191(11):1273-86. doi: 10.1164/rccm.201412-2291OC.
8
Heterozygous null bone morphogenetic protein receptor type 2 mutations promote SRC kinase-dependent caveolar trafficking defects and endothelial dysfunction in pulmonary arterial hypertension.杂合性骨形态发生蛋白受体2型无效突变促进Src激酶依赖性小窝转运缺陷及肺动脉高压中的内皮功能障碍。
J Biol Chem. 2015 Jan 9;290(2):960-71. doi: 10.1074/jbc.M114.591057. Epub 2014 Nov 19.
9
Characterization of a caveolin-1 mutation associated with both pulmonary arterial hypertension and congenital generalized lipodystrophy.一种与肺动脉高压和先天性全身性脂肪营养不良相关的小窝蛋白-1突变的特征分析。
Traffic. 2016 Dec;17(12):1297-1312. doi: 10.1111/tra.12452. Epub 2016 Nov 2.
10
Trapping of BMP receptors in distinct membrane domains inhibits their function in pulmonary arterial hypertension.BMP 受体在不同的膜域中被捕获会抑制其在肺动脉高压中的功能。
Am J Physiol Lung Cell Mol Physiol. 2011 Aug;301(2):L218-27. doi: 10.1152/ajplung.00300.2010. Epub 2011 May 27.

引用本文的文献

1
Caveolin-1 Deficiency in Macrophages Alleviates Carbon Tetra-Chloride-Induced Acute Liver Injury in Mice.巨噬细胞中窖蛋白-1缺乏减轻四氯化碳诱导的小鼠急性肝损伤
Int J Mol Sci. 2025 May 20;26(10):4903. doi: 10.3390/ijms26104903.
2
Pulmonary Hypertension: Molecular Mechanisms and Clinical Studies.肺动脉高压：分子机制与临床研究
MedComm (2020). 2025 Mar 10;6(3):e70134. doi: 10.1002/mco2.70134. eCollection 2025 Mar.
3
miR-125b differentially impacts mineralization in dexamethasone and calcium-treated human mesenchymal stem cells.

本文引用的文献

1
2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension.2022年欧洲心脏病学会/欧洲呼吸学会肺动脉高压诊断和治疗指南。
Eur Heart J. 2022 Oct 11;43(38):3618-3731. doi: 10.1093/eurheartj/ehac237.
2
Sotatercept analog suppresses inflammation to reverse experimental pulmonary arterial hypertension.索特瑞塞特类似物抑制炎症反应逆转实验性肺动脉高压。
Sci Rep. 2022 May 12;12(1):7803. doi: 10.1038/s41598-022-11435-x.
3
Generation of dystrophin short product-specific tag-insertion mouse: distinct Dp71 glycoprotein complexes at inhibitory postsynapse and glia limitans.
微小RNA-125b对经地塞米松和钙处理的人间充质干细胞的矿化作用有不同影响。
Mol Ther Nucleic Acids. 2025 Jan 3;36(1):102446. doi: 10.1016/j.omtn.2024.102446. eCollection 2025 Mar 11.
4
Mechanosensory entities and functionality of endothelial cells.内皮细胞的机械感觉实体与功能
Front Cell Dev Biol. 2024 Oct 23;12:1446452. doi: 10.3389/fcell.2024.1446452. eCollection 2024.
5
ALK1 Signaling in Human Cardiac Progenitor Cells Promotes a Pro-angiogenic Secretome.人类心脏祖细胞中的ALK1信号传导促进促血管生成分泌组。
J Cell Signal. 2024;5(3):122-142. doi: 10.33696/signaling.5.119.
6
The critical roles of caveolin-1 in lung diseases.小窝蛋白-1在肺部疾病中的关键作用。
Front Pharmacol. 2024 Sep 24;15:1417834. doi: 10.3389/fphar.2024.1417834. eCollection 2024.
生成肌营养不良蛋白短产物特异性标签插入小鼠：抑制性突触和胶质界处不同的 Dp71 糖蛋白复合物。
Cell Mol Life Sci. 2022 Jan 30;79(2):109. doi: 10.1007/s00018-022-04151-2.
4
Requirement of Cavin-2 for the expression and stability of IRβ in adequate adipocyte differentiation.Cavin-2 对 IRβ 在充分的脂肪细胞分化中的表达和稳定性的需求。
Mol Metab. 2022 Jan;55:101416. doi: 10.1016/j.molmet.2021.101416. Epub 2021 Dec 9.
5
Isolation of Primary Mouse Lung Endothelial Cells.原代鼠肺内皮细胞的分离。
J Vis Exp. 2021 Nov 10(177). doi: 10.3791/63253.
6
COMPERA 2.0: a refined four-stratum risk assessment model for pulmonary arterial hypertension.COMPERA 2.0：一种改良的肺动脉高压四层风险评估模型。
Eur Respir J. 2022 Jul 7;60(1). doi: 10.1183/13993003.02311-2021. Print 2022 Jul.
7
Critical Role of Caveolin-1 Loss/Dysfunction in Pulmonary Hypertension.窖蛋白-1 缺失/功能障碍在肺动脉高压中的关键作用。
Med Sci (Basel). 2021 Sep 22;9(4):58. doi: 10.3390/medsci9040058.
8
Protocols for endothelial cell isolation from mouse tissues: brain, choroid, lung, and muscle.从鼠组织中分离内皮细胞的方案：脑、脉络丛、肺和肌肉。
STAR Protoc. 2021 Sep 14;2(3):100508. doi: 10.1016/j.xpro.2021.100508. eCollection 2021 Sep 17.
9
Heat shock protein 70 attenuates hypoxia‑induced apoptosis of pulmonary microvascular endothelial cells isolated from neonatal rats.热休克蛋白 70 减轻新生大鼠肺微血管内皮细胞缺氧诱导的凋亡。
Mol Med Rep. 2021 Oct;24(4). doi: 10.3892/mmr.2021.12327. Epub 2021 Jul 30.
10
Isolation of Microvascular Endothelial Cells.微血管内皮细胞的分离
Bio Protoc. 2018 Jun 20;8(12):e2886. doi: 10.21769/BioProtoc.2886.