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

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.