Vasculature is an important component of the neural stem cell niche in brain. It regulates neural stem/progenitor (NS/P) cell self-renewal, differentiation and migration. In the neurogenic niches of adult brain, NS/P cells lie close to blood vessels and proliferating NS/P cells frequently contact the vasculature. In the present study we showed that NS/P cells in co-culture with brain endothelial (bEND) cells activated endothelial G-proteins and p38 mitogenic activated protein kinase (p38MAPK), and stimulated cytokine/chemokine expression. These NS/P cell-induced endothelial responses took place during NS/P cell and bEND cell direct contact and were critically dependent on the expression of the type II transmembrane serine protease matriptase (MTP) by NS/P cells, since knocking down of MTP in NS/P cells impaired and re-expression of MTP restored their ability to induce endothelial cytokine/chemokine expression, p38MAPK or G-protein activation. Cholera toxin blocked NS/P cell-induced endothelial responses suggesting the endothelial G-protein activated by NS/P MTP is in the Gs subfamily. Addition of p38MAPK inhibitor impaired NS/P cell-induced endothelial cytokine/ chemokine expression. The known G-protein coupled receptor substrate of MTP, protease activated receptor 2, was not involved in this system. These results revealed a novel signaling pathway in neural stem cell vascular niches that is mediated by neural MTP and endothelial Gs-protein signaling at the cell-cell interface. This is the first report of direct cell-cell signaling between NS/P and bEND cells.
Date:
2012-06
Relation:
Journal of Biological Chemistry. 2012 Jun;287(27):22497-22508.
