• 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

sonic 刺猬基因递送至啮齿动物心脏通过诱导型一氧化氮合酶/轴突导向因子-1/蛋白激酶 C 通路促进血管生成。

Sonic Hedgehog gene delivery to the rodent heart promotes angiogenesis via iNOS/netrin-1/PKC pathway.

机构信息

Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, Ohio, United States of America.

出版信息

PLoS One. 2010 Jan 5;5(1):e8576. doi: 10.1371/journal.pone.0008576.

DOI:10.1371/journal.pone.0008576
PMID:20052412
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2797399/
Abstract

BACKGROUND

We hypothesized that genetic modification of mesenchymal stem cells (MSCs) with Sonic Hedgehog (Shh) transgene, a morphogen during embryonic development and embryonic and adult stem cell growth, improved their survival and angiogenic potential in the ischemic heart via iNOS/netrin/PKC pathway.

METHODS/PRINCIPAL FINDINGS: MSCs from young Fisher-344 rat bone marrow were purified and transfected with pCMV Shh plasmid ((Shh)MSCs). Immunofluorescence, RT-PCR and Western blotting showed higher expression of Shh in (Shh)MSCs which also led to increased expression of angiogenic and pro-survival growth factors in (Shh)MSCs. Significantly improved migration and tube formation was seen in (Shh)MSCs as compared to empty vector transfected MSCs ((Emp)MSCs). Significant upregulation of netrin-1 and iNOS was observed in (Shh)MSCs in PI3K independent but PKC dependent manner. For in vivo studies, acute myocardial infarction model was developed in Fisher-344 rats. The animals were grouped to receive 70 microl basal DMEM without cells (group-1) or containing 1x10(6) (Emp)MSCs (group-2) and (Shh)MSCs (group-3). Group-4 received recombinant netrin-1 protein injection into the infarcted heart. FISH and sry-quantification revealed improved survival of (Shh)MSCs post engraftment. Histological studies combined with fluorescent microspheres showed increased density of functionally competent blood vessels in group-3 and group-4. Echocardiography showed significantly preserved heart function indices post engraftment with (Shh)MSCs in group-3 animals.

CONCLUSIONS/SIGNIFICANCE: Reprogramming of stem cells with Shh maximizes their survival and angiogenic potential in the heart via iNOS/netrin-1/PKC signaling.

摘要

背景

我们假设，通过 iNOS/netrin/PKC 通路，将 Sonic Hedgehog（Shh）基因转染到间充质干细胞（MSCs）中，这种基因是胚胎发育和胚胎及成体干细胞生长过程中的一种形态发生素，可以改善其在缺血心脏中的存活和血管生成能力。

方法/主要发现：从小鼠骨髓中分离纯化的年轻 Fisher-344 大鼠间充质干细胞（MSCs），并用 pCMV Shh 质粒（(Shh)MSCs）转染。免疫荧光、RT-PCR 和 Western blot 显示，（Shh）MSCs 中 Shh 的表达更高，并且还导致了血管生成和生存相关生长因子在（Shh）MSCs 中的表达增加。与空载体转染的 MSCs((Emp)MSCs)相比，（Shh）MSCs 的迁移和管状结构形成明显增加。在 PI3K 非依赖性但 PKC 依赖性方式下，（Shh）MSCs 中 netrin-1 和 iNOS 的表达显著上调。在体内研究中，在 Fisher-344 大鼠中建立了急性心肌梗死模型。将动物分为四组，分别接受 70 微升无细胞基础 DMEM（第 1 组）或含 1x10(6)(Emp)MSCs（第 2 组）和（Shh）MSCs（第 3 组）。第 4 组接受重组 netrin-1 蛋白注射到梗死心脏。FISH 和 sry 定量分析显示，（Shh）MSCs 植入后的存活率提高。组织学研究结合荧光微球显示，第 3 组和第 4 组中功能上有竞争力的血管密度增加。心脏超声心动图显示，第 3 组动物的（Shh）MSCs 移植后心功能指标显著改善。

结论/意义：Shh 对干细胞进行重编程，通过 iNOS/netrin-1/PKC 信号通路最大程度地提高了它们在心脏中的存活和血管生成能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/172d27701e8e/pone.0008576.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/63d87ac88b2f/pone.0008576.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/6f7d41f83379/pone.0008576.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/d6e76a80fae3/pone.0008576.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/e672aeb9e47d/pone.0008576.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/57a75a7a00ac/pone.0008576.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/26a710030ff4/pone.0008576.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/3220f1b8581f/pone.0008576.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/172d27701e8e/pone.0008576.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/63d87ac88b2f/pone.0008576.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/6f7d41f83379/pone.0008576.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/d6e76a80fae3/pone.0008576.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/e672aeb9e47d/pone.0008576.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/57a75a7a00ac/pone.0008576.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/26a710030ff4/pone.0008576.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/3220f1b8581f/pone.0008576.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda0/2797399/172d27701e8e/pone.0008576.g008.jpg

相似文献

1
Sonic Hedgehog gene delivery to the rodent heart promotes angiogenesis via iNOS/netrin-1/PKC pathway. sonic 刺猬基因递送至啮齿动物心脏通过诱导型一氧化氮合酶/轴突导向因子-1/蛋白激酶 C 通路促进血管生成。
PLoS One. 2010 Jan 5;5(1):e8576. doi: 10.1371/journal.pone.0008576.
2
Netrin-1 ameliorates myocardial infarction-induced myocardial injury: mechanisms of action in rats and diabetic mice.Netrin-1改善心肌梗死所致的心肌损伤：大鼠和糖尿病小鼠中的作用机制
Hum Gene Ther. 2014 Sep;25(9):787-97. doi: 10.1089/hum.2014.021. Epub 2014 Jun 18.
3
Cytoprotective and proangiogenic activity of ex-vivo netrin-1 transgene overexpression protects the heart against ischemia/reperfusion injury.外源性 netrin-1 过表达的细胞保护和促血管生成活性可保护心脏免受缺血/再灌注损伤。
Stem Cells Dev. 2012 Jul 1;21(10):1769-78. doi: 10.1089/scd.2011.0475. Epub 2011 Nov 11.
4
Sonic hedgehog induces angiogenesis via Rho kinase-dependent signaling in endothelial cells. Sonic hedgehog 通过内皮细胞中 Rho 激酶依赖性信号诱导血管生成。
J Mol Cell Cardiol. 2010 Sep;49(3):490-8. doi: 10.1016/j.yjmcc.2010.05.003. Epub 2010 May 15.
5
Effects of myocardial transplantation of marrow mesenchymal stem cells transfected with vascular endothelial growth factor for the improvement of heart function and angiogenesis after myocardial infarction.转染血管内皮生长因子的骨髓间充质干细胞心肌移植对改善心肌梗死后心脏功能及血管生成的作用
Cardiology. 2007;107(1):17-29. doi: 10.1159/000093609. Epub 2006 May 24.
6
[Effects of myocardial transplantation of mesenchymal stem cells transfected with vascular endothelial factor gene on improvement of heart function and angiogenesis after myocardial infarction: experiment with rats].血管内皮生长因子基因转染间充质干细胞心肌移植对心肌梗死后心功能改善及血管生成的影响：大鼠实验
Zhonghua Yi Xue Za Zhi. 2006 Apr 18;86(15):1027-34.
7
Netrin-1 promotes mesenchymal stem cell revascularization of limb ischaemia.Netrin-1促进肢体缺血的间充质干细胞血管再生。
Diab Vasc Dis Res. 2016 Mar;13(2):145-56. doi: 10.1177/1479164115611594. Epub 2016 Jan 27.
8
AKT-modified autologous intracoronary mesenchymal stem cells prevent remodeling and repair in swine infarcted myocardium.AKT 修饰的自体冠状动脉间充质干细胞预防猪梗死心肌的重构和修复。
Chin Med J (Engl). 2010 Jul;123(13):1702-8.
9
AAV-mediated netrin-1 overexpression increases peri-infarct blood vessel density and improves motor function recovery after experimental stroke.腺相关病毒介导的轴突导向因子 1 过表达增加实验性卒中后梗死周围血管密度并改善运动功能恢复。
Neurobiol Dis. 2011 Oct;44(1):73-83. doi: 10.1016/j.nbd.2011.06.006. Epub 2011 Jun 25.
10
Effect of Recombinant Netrin-1 Protein Combined with Peripheral Blood Mesenchymal Stem Cells on Angiogenesis in Rats with Arteriosclerosis Obliterans.重组轴突导向因子 1 蛋白联合外周血间充质干细胞对动脉硬化闭塞症大鼠血管生成的影响。
Biomed Res Int. 2022 Jul 26;2022:3361605. doi: 10.1155/2022/3361605. eCollection 2022.

引用本文的文献

1
Hypoxia-Elicited Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Alleviate Myocardial Infarction by Promoting Angiogenesis through the miR-214/Sufu Pathway.缺氧诱导间充质干细胞衍生的小细胞外囊泡通过miR-214/Sufu途径促进血管生成减轻心肌梗死
Stem Cells Int. 2023 Jan 13;2023:1662182. doi: 10.1155/2023/1662182. eCollection 2023.
2
Netrin-1 promotes the vasculogenic capacity of human adipose-derived stem cells.神经导向因子 1 可增强人脂肪来源干细胞的血管生成能力。
Cell Tissue Bank. 2023 Jun;24(2):357-367. doi: 10.1007/s10561-022-10038-0. Epub 2022 Oct 12.
3
Signaling pathways and targeted therapy for myocardial infarction.

本文引用的文献

1
Microparticles harboring Sonic Hedgehog promote angiogenesis through the upregulation of adhesion proteins and proangiogenic factors.携带音猬因子的微粒通过上调黏附蛋白和促血管生成因子来促进血管生成。
Carcinogenesis. 2009 Apr;30(4):580-8. doi: 10.1093/carcin/bgp030. Epub 2009 Jan 23.
2
IGF-1-overexpressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1alpha/CXCR4 signaling to promote myocardial repair.过表达胰岛素样生长因子-1的间充质干细胞通过旁分泌激活基质细胞衍生因子-1α/趋化因子受体4信号通路加速骨髓干细胞动员，从而促进心肌修复。
Circ Res. 2008 Nov 21;103(11):1300-8. doi: 10.1161/CIRCRESAHA.108.186742. Epub 2008 Oct 23.
3
心肌梗死的信号通路和靶向治疗。
Signal Transduct Target Ther. 2022 Mar 10;7(1):78. doi: 10.1038/s41392-022-00925-z.
4
A Synopsis of Signaling Crosstalk of Pericytes and Endothelial Cells in Salivary Gland.唾液腺中周细胞与内皮细胞信号串扰概述
Dent J (Basel). 2021 Dec 1;9(12):144. doi: 10.3390/dj9120144.
5
Sonic Hedgehog upregulation does not enhance the survival and engraftment of stem cell-derived cardiomyocytes in infarcted hearts. sonic Hedgehog 上调并不能增强干细胞来源的心肌细胞在梗死心脏中的存活和植入。
PLoS One. 2020 Jan 16;15(1):e0227780. doi: 10.1371/journal.pone.0227780. eCollection 2020.
6
The Hedgehog Signaling Pathway in Ischemic Tissues.缺血组织中的 Hedgehog 信号通路。
Int J Mol Sci. 2019 Oct 24;20(21):5270. doi: 10.3390/ijms20215270.
7
Increased expression of Sonic hedgehog restores diabetic endothelial progenitor cells and improves cardiac repair after acute myocardial infarction in diabetic mice.Sonic hedgehog 的过表达可恢复糖尿病小鼠急性心肌梗死后的内皮祖细胞，并改善心脏修复。
Int J Mol Med. 2019 Sep;44(3):1091-1105. doi: 10.3892/ijmm.2019.4277. Epub 2019 Jul 16.
8
Role of Hedgehog Signaling in Vasculature Development, Differentiation, and Maintenance. hedgehog 信号在血管发育、分化和维持中的作用。
Int J Mol Sci. 2019 Jun 24;20(12):3076. doi: 10.3390/ijms20123076.
9
Sonic hedgehog promotes endothelial differentiation of bone marrow mesenchymal stem cells via VEGF-D.音猬因子通过血管内皮生长因子-D促进骨髓间充质干细胞向内皮细胞分化。
J Thorac Dis. 2018 Sep;10(9):5476-5488. doi: 10.21037/jtd.2018.09.50.
10
Plasma proteomic analysis reveals altered protein abundances in cardiovascular disease.血浆蛋白质组分析揭示了心血管疾病中蛋白质丰度的改变。
J Transl Med. 2018 Apr 17;16(1):104. doi: 10.1186/s12967-018-1476-9.
Sonic hedgehog regulates angiogenesis and myogenesis during post-natal skeletal muscle regeneration.
Sonic hedgehog 调控出生后骨骼肌再生过程中的血管生成和肌生成。
J Cell Mol Med. 2009 Aug;13(8B):2424-2435. doi: 10.1111/j.1582-4934.2008.00440.x. Epub 2008 Jul 26.
4
Protein kinase C is an important signaling mediator associated with motility of intact sea urchin spermatozoa.蛋白激酶C是一种与完整海胆精子运动相关的重要信号传导介质。
J Exp Biol. 2007 Nov;210(Pt 22):4053-64. doi: 10.1242/jeb.007013.
5
Bone marrow cells adopt the cardiomyogenic fate in vivo.骨髓细胞在体内会转变为心肌生成命运。
Proc Natl Acad Sci U S A. 2007 Nov 6;104(45):17783-8. doi: 10.1073/pnas.0706406104. Epub 2007 Oct 26.
6
Sonic hedgehog stimulates mouse embryonic stem cell proliferation by cooperation of Ca2+/protein kinase C and epidermal growth factor receptor as well as Gli1 activation.音猬因子通过Ca2+/蛋白激酶C与表皮生长因子受体的协同作用以及Gli1激活来刺激小鼠胚胎干细胞增殖。
Stem Cells. 2007 Dec;25(12):3069-80. doi: 10.1634/stemcells.2007-0550. Epub 2007 Sep 27.
7
Transcoronary transplantation of progenitor cells after myocardial infarction.心肌梗死后祖细胞的经冠状动脉移植
N Engl J Med. 2006 Sep 21;355(12):1222-32. doi: 10.1056/NEJMoa051779.
8
Supportive interaction between cell survival signaling and angiocompetent factors enhances donor cell survival and promotes angiomyogenesis for cardiac repair.细胞存活信号与血管生成能力因子之间的支持性相互作用可提高供体细胞的存活率，并促进血管生成性肌生成以修复心脏。
Circ Res. 2006 Sep 29;99(7):776-84. doi: 10.1161/01.RES.0000244687.97719.4f. Epub 2006 Sep 7.
9
Adenoviral-mediated gene transfer of nitric oxide synthase isoforms and vascular cell proliferation.腺病毒介导的一氧化氮合酶亚型基因转移与血管细胞增殖
J Vasc Res. 2006;43(5):462-72. doi: 10.1159/000095163. Epub 2006 Aug 17.
10
Netrins promote developmental and therapeutic angiogenesis.Netrin蛋白促进发育性血管生成和治疗性血管生成。
Science. 2006 Aug 4;313(5787):640-4. doi: 10.1126/science.1124704. Epub 2006 Jun 29.