ADAMTS18<sup>+</sup> villus tip telocytes maintain a polarized VEGFA signaling domain and fenestrations in nutrient-absorbing intestinal blood vessels.

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License: CC BY 4.0
Serval ID
serval:BIB_AC4B62DD6AED
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
ADAMTS18<sup>+</sup> villus tip telocytes maintain a polarized VEGFA signaling domain and fenestrations in nutrient-absorbing intestinal blood vessels.
Journal
Nature communications
Author(s)
Bernier-Latmani J., Mauri C., Marcone R., Renevey F., Durot S., He L., Vanlandewijck M., Maclachlan C., Davanture S., Zamboni N., Knott G.W., Luther S.A., Betsholtz C., Delorenzi M., Brisken C., Petrova T.V.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
09/07/2022
Peer-reviewed
Oui
Volume
13
Number
1
Pages
3983
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
The small intestinal villus tip is the first point of contact for lumen-derived substances including nutrients and microbial products. Electron microscopy studies from the early 1970s uncovered unusual spatial organization of small intestinal villus tip blood vessels: their exterior, epithelial-facing side is fenestrated, while the side facing the villus stroma is non-fenestrated, covered by pericytes and harbors endothelial nuclei. Such organization optimizes the absorption process, however the molecular mechanisms maintaining this highly specialized structure remain unclear. Here we report that perivascular LGR5 <sup>+</sup> villus tip telocytes (VTTs) are necessary for maintenance of villus tip endothelial cell polarization and fenestration by sequestering VEGFA signaling. Mechanistically, unique VTT expression of the protease ADAMTS18 is necessary for VEGFA signaling sequestration through limiting fibronectin accumulation. Therefore, we propose a model in which LGR5 <sup>+</sup> ADAMTS18 <sup>+</sup> telocytes are necessary to maintain a "just-right" level and location of VEGFA signaling in intestinal villus blood vasculature to ensure on one hand the presence of sufficient endothelial fenestrae, while avoiding excessive leakiness of the vessels and destabilization of villus tip epithelial structures.
Keywords
Duodenum, Intestinal Mucosa/metabolism, Intestines, Nutrients, Telocytes
Pubmed
Web of science
Open Access
Yes
Create date
18/07/2022 10:50
Last modification date
22/07/2022 6:38
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