Airway basal cell vascular endothelial growth factor-mediated cross-talk regulates endothelial cell-dependent growth support of human airway basal cells. Academic Article uri icon

Overview

MeSH

  • Blotting, Western
  • Cell Proliferation
  • Cells, Cultured
  • DNA Primers
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Protein Isoforms
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction

MeSH Major

  • Endothelial Cells
  • Paracrine Communication
  • Receptor Cross-Talk
  • Respiratory Mucosa
  • Signal Transduction
  • Vascular Endothelial Growth Factor A

abstract

  • The human airway epithelium is a pseudostratified heterogenous layer comprised of ciliated, secretory, intermediate, and basal cells. As the stem/progenitor population of the airway epithelium, airway basal cells differentiate into ciliated and secretory cells to replenish the airway epithelium during physiological turnover and repair. Transcriptome analysis of airway basal cells revealed high expression of vascular endothelial growth factor A (VEGFA), a gene not typically associated with the function of this cell type. Using cultures of primary human airway basal cells, we demonstrate that basal cells express all of the three major isoforms of VEGFA (121, 165 and 189) but lack functional expression of the classical VEGFA receptors VEGFR1 and VEGFR2. The VEGFA is actively secreted by basal cells and while it appears to have no direct autocrine function on basal cell growth and proliferation, it functions in a paracrine manner to activate MAPK signaling cascades in endothelium via VEGFR2-dependent signaling pathways. Using a cytokine- and serum-free co-culture system of primary human airway basal cells and human endothelial cells revealed that basal cell-secreted VEGFA activated endothelium to express mediators that, in turn, stimulate and support basal cell proliferation and growth. These data demonstrate novel VEGFA-mediated cross-talk between airway basal cells and endothelium, the purpose of which is to modulate endothelial activation and in turn stimulate and sustain basal cell growth.

publication date

  • July 2012

has subject area

  • Blotting, Western
  • Cell Proliferation
  • Cells, Cultured
  • DNA Primers
  • Endothelial Cells
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Paracrine Communication
  • Protein Isoforms
  • Real-Time Polymerase Chain Reaction
  • Receptor Cross-Talk
  • Respiratory Mucosa
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Vascular Endothelial Growth Factor A

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3633460

Digital Object Identifier (DOI)

  • 10.1007/s00018-012-0922-8

PubMed ID

  • 22382924

Additional Document Info

start page

  • 2217

end page

  • 2231

volume

  • 69

number

  • 13