The Petrova Lab identifies a specialized subset of perivascular fibroblasts that organize extracellular matrix to compartmentalize angiogenic VEGF-A signaling in the intestinal villi.
VEGF-A signaling promotes endothelial proliferation, migration and sprouting and is essential for growth of new blood vessels during tumorigenesis or tissue regeneration. A less known but equally important function of VEGF-A in normal tissues is maintenance of endothelial fenestra, small pores in vessels, which are necessary for uptake of secreted hormones and nutrients in endocrine organs and intestine. A proper balance or “just-right” level and location of VEGFA signaling is necessary to ensure the presence of sufficient endothelial fenestrae while avoiding excessive leakiness of the vessels and destabilization of the vascular tree because of a full-blown angiogenic response.
Researchers in the Petrova Lab identified a novel subpopulation of intestinal villus perivascular fibroblasts that maintain such an equilibrium by producing both the protease ADAMTS18 and its substrate, VEGFA-retaining extracellular matrix component fibronectin. Such organization limits the spread of ECM-bound VEGFA and localizes endothelial fenestra to the areas of nutrient release from intestinal epithelial cells.
The research* was conducted in collaboration with EPFL, SIB, Karolinska Institutet and Uppsala University, Sweden.
The project was supported by the Swiss National Science Foundation (SNSF).
*ADAMTS18 + villus tip telocytes maintain a polarized VEGFA signaling domain and fenestrations in nutrient-absorbing intestinal blood vessels