Endothelial MMP14 is required for endothelial-dependent growth support of human airway basal cells.

Publication Type	Academic Article
Authors	Ding B, Gomi K, Rafii S, Crystal R, Walters M
Journal	J Cell Sci
Volume	128
Issue	16
Pagination	2983-8
Date Published	06/26/2015
ISSN	1477-9137
Keywords	Basement Membrane, Endothelial Cells, Matrix Metalloproteinase 14, Paracrine Communication
Abstract	Human airway basal cells are the stem (or progenitor) population of the airway epithelium, and play a central role in anchoring the epithelium to the basement membrane. The anatomic position of basal cells allows for potential paracrine signaling between them and the underlying non-epithelial stromal cells. In support of this, we have previously demonstrated that endothelial cells support growth of basal cells during co-culture through vascular endothelial growth factor A (VEGFA)-mediated signaling. Building on these findings, we found, by RNA sequencing analysis, that basal cells expressed multiple fibroblast growth factor (FGF) ligands (FGF2, FGF5, FGF11 and FGF13) and that only FGF2 and FGF5 were capable of functioning in a paracrine manner to activate classical FGF receptor (FGFR) signaling. Antibody-mediated blocking of FGFR1 during basal-cell-endothelial-cell co-culture significantly reduced the endothelial-cell-dependent basal cell growth. Stimulation of endothelial cells with basal-cell-derived growth factors induced endothelial cell expression of matrix metallopeptidase 14 (MMP14), and short hairpin RNA (shRNA)-mediated knockdown of endothelial cell MMP14 significantly reduced the endothelial-cell-dependent growth of basal cells. Overall, these data characterize a new growth-factor-mediated reciprocal 'crosstalk' between human airway basal cells and endothelial cells that regulates proliferation of basal cells.
DOI	10.1242/jcs.168179
PubMed ID	26116571
PubMed Central ID	PMC4541042