Niche-associated Type IV collagen promotes GLP-1/Notch receptor activation in the C. elegans germline.

IF 15.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Nature Communications Pub Date : 2025-10-23 DOI:10.1038/s41467-025-64394-y

Pier-Olivier Martel,Rustelle Janse van Vuuren,Julia Degrémont,Sarah Turmel-Couture,Armi M Chaudhari,Eden Dologuele,Lucie Beaulieu,Alexandre Clouet,Patrick Narbonne

{"title":"Niche-associated Type IV collagen promotes GLP-1/Notch receptor activation in the C. elegans germline.","authors":"Pier-Olivier Martel,Rustelle Janse van Vuuren,Julia Degrémont,Sarah Turmel-Couture,Armi M Chaudhari,Eden Dologuele,Lucie Beaulieu,Alexandre Clouet,Patrick Narbonne","doi":"10.1038/s41467-025-64394-y","DOIUrl":null,"url":null,"abstract":"Basement membranes are thin and dense proteinaceous layers that surround tissues to maintain their structure. With age, chronic inflammation typically stiffens this basement membrane through a phenomenon called fibrosis, which is reflected by increasing levels of the basement membrane's main structural component, type IV collagen (COL IV). Tissue fibrosis and elevated Notch signalling are two co-occurring hallmarks of many inflammation-linked diseases, including cancer, but their in vivo relationship has not been clearly defined. Here we show that EMB-9/COL IV accumulation around the C. elegans germline stem cell niche promotes GLP-1/Notch receptor activation in germline stem cells. Moreover, we find that contrasting with previous beliefs, reducing GLP-1/Notch activity in vivo leads to a generalized dramatic increase in EMB-9/COL IV levels, and thereby promotes fibrosis. The generalized fibrosis that comes along with inflammaging may therefore act as a root cause for cancer by promoting Notch signalling, and perhaps other ligand-receptor interactions.","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"1 1","pages":"9363"},"PeriodicalIF":15.7000,"publicationDate":"2025-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-025-64394-y","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

Basement membranes are thin and dense proteinaceous layers that surround tissues to maintain their structure. With age, chronic inflammation typically stiffens this basement membrane through a phenomenon called fibrosis, which is reflected by increasing levels of the basement membrane's main structural component, type IV collagen (COL IV). Tissue fibrosis and elevated Notch signalling are two co-occurring hallmarks of many inflammation-linked diseases, including cancer, but their in vivo relationship has not been clearly defined. Here we show that EMB-9/COL IV accumulation around the C. elegans germline stem cell niche promotes GLP-1/Notch receptor activation in germline stem cells. Moreover, we find that contrasting with previous beliefs, reducing GLP-1/Notch activity in vivo leads to a generalized dramatic increase in EMB-9/COL IV levels, and thereby promotes fibrosis. The generalized fibrosis that comes along with inflammaging may therefore act as a root cause for cancer by promoting Notch signalling, and perhaps other ligand-receptor interactions.

查看原文本刊更多论文

生态位相关的IV型胶原促进秀丽隐杆线虫种系中GLP-1/Notch受体的激活。

基底膜是包围组织以维持其结构的薄而致密的蛋白质层。随着年龄的增长，慢性炎症通常通过一种称为纤维化的现象使基底膜变硬，这反映在基底膜主要结构成分IV型胶原蛋白（COL IV）水平的增加上。组织纤维化和Notch信号升高是许多炎症相关疾病（包括癌症）的两个共同发生的标志，但它们在体内的关系尚未明确定义。本研究表明，EMB-9/COL IV在秀丽隐杆线虫种系干细胞生态位周围的积累促进了种系干细胞中GLP-1/Notch受体的激活。此外，我们发现与之前的观点相反，体内GLP-1/Notch活性的降低会导致EMB-9/COL IV水平的普遍急剧增加，从而促进纤维化。因此，伴随炎症而来的全身性纤维化可能通过促进Notch信号传导以及其他配体与受体的相互作用而成为癌症的根本原因。

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

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.