Epithelial tubule interconnection driven by HGF-Met signaling in the kidney

IF 9.4 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Isabel López-García, Sunhee Oh, Christopher Chaney, Jun Tsunezumi, Iain Drummond, Leif Oxburgh, Thomas J. Carroll, Denise K. Marciano
{"title":"Epithelial tubule interconnection driven by HGF-Met signaling in the kidney","authors":"Isabel López-García, Sunhee Oh, Christopher Chaney, Jun Tsunezumi, Iain Drummond, Leif Oxburgh, Thomas J. Carroll, Denise K. Marciano","doi":"10.1073/pnas.2416887121","DOIUrl":null,"url":null,"abstract":"The formation of functional epithelial tubules is critical for the development and maintenance of many organ systems. While the mechanisms of tubule formation by epithelial cells are well studied, the process of tubule anastomosis—where tubules connect to form a continuous network—remains poorly understood. In this study, we utilized single-cell RNA sequencing to analyze embryonic mouse kidney tubules undergoing anastomosis. Our analysis identified hepatocyte growth factor (HGF) as a key potential mediator of this process. To investigate this further, we developed an assay using epithelial spheroids with fluorescently tagged apical surfaces, allowing us to visualize and quantify tubule–tubule connections. Our results demonstrate that HGF promotes tubule anastomosis, and it does so through the MAPK signaling pathway and MMPs, independently of cell proliferation. Remarkably, treatment with HGF and collagenase was sufficient to induce tubule anastomosis in embryonic mouse kidneys. These findings provide a foundational understanding of how to enhance the formation of functional tubular networks. This has significant clinical implications for the use of in vitro–grown kidney tissues in transplant medicine, potentially improving the success and integration of transplanted tissues.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"77 1","pages":""},"PeriodicalIF":9.4000,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proceedings of the National Academy of Sciences of the United States of America","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1073/pnas.2416887121","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0

Abstract

The formation of functional epithelial tubules is critical for the development and maintenance of many organ systems. While the mechanisms of tubule formation by epithelial cells are well studied, the process of tubule anastomosis—where tubules connect to form a continuous network—remains poorly understood. In this study, we utilized single-cell RNA sequencing to analyze embryonic mouse kidney tubules undergoing anastomosis. Our analysis identified hepatocyte growth factor (HGF) as a key potential mediator of this process. To investigate this further, we developed an assay using epithelial spheroids with fluorescently tagged apical surfaces, allowing us to visualize and quantify tubule–tubule connections. Our results demonstrate that HGF promotes tubule anastomosis, and it does so through the MAPK signaling pathway and MMPs, independently of cell proliferation. Remarkably, treatment with HGF and collagenase was sufficient to induce tubule anastomosis in embryonic mouse kidneys. These findings provide a foundational understanding of how to enhance the formation of functional tubular networks. This has significant clinical implications for the use of in vitro–grown kidney tissues in transplant medicine, potentially improving the success and integration of transplanted tissues.
肾中HGF-Met信号驱动的上皮小管互连
功能性上皮小管的形成对许多器官系统的发育和维持至关重要。虽然上皮细胞形成小管的机制已经得到了很好的研究,但小管吻合的过程(小管连接形成一个连续的网络)仍然知之甚少。在这项研究中,我们利用单细胞RNA测序分析胚胎小鼠肾小管进行吻合。我们的分析确定肝细胞生长因子(HGF)是这一过程的关键潜在介质。为了进一步研究这一点,我们开发了一种使用具有荧光标记的顶端表面的上皮球体的检测方法,使我们能够可视化和量化小管与小管之间的连接。我们的研究结果表明,HGF通过MAPK信号通路和MMPs促进小管吻合,而不依赖于细胞增殖。值得注意的是,HGF和胶原酶足以诱导小鼠胚胎肾小管吻合。这些发现为如何增强功能性管状网络的形成提供了基础的理解。这对于在移植医学中使用体外培养的肾脏组织具有重要的临床意义,有可能提高移植组织的成功率和整合。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
19.00
自引率
0.90%
发文量
3575
审稿时长
2.5 months
期刊介绍: The Proceedings of the National Academy of Sciences (PNAS), a peer-reviewed journal of the National Academy of Sciences (NAS), serves as an authoritative source for high-impact, original research across the biological, physical, and social sciences. With a global scope, the journal welcomes submissions from researchers worldwide, making it an inclusive platform for advancing scientific knowledge.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信