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

Overview

MeSH

  • Cell Proliferation
  • Coculture Techniques
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 5
  • Fibroblast Growth Factors
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Ligands
  • Receptor, Fibroblast Growth Factor, Type 1
  • Stromal Cells

MeSH Major

  • 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. © 2015. Published by The Company of Biologists Ltd.

publication date

  • August 15, 2015

has subject area

  • Basement Membrane
  • Cell Proliferation
  • Coculture Techniques
  • Endothelial Cells
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 5
  • Fibroblast Growth Factors
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Ligands
  • Matrix Metalloproteinase 14
  • Paracrine Communication
  • Receptor, Fibroblast Growth Factor, Type 1
  • Stromal Cells

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4541042

Digital Object Identifier (DOI)

  • 10.1242/jcs.168179

PubMed ID

  • 26116571

Additional Document Info

start page

  • 2983

end page

  • 2988

volume

  • 128

number

  • 16