Airway basal cell vascular endothelial growth factor-mediated cross-talk regulates endothelial cell-dependent growth support of human airway basal cells

Giacomo Curradi, Matthew S. Walters, Bi Sen Ding, Shahin Rafii, Neil R. Hackett, Ronald Crystal

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2217-2231
Number of pages15
JournalCellular and Molecular Life Sciences
Volume69
Issue number13
DOIs
Publication statusPublished - 1 Jul 2012
Externally publishedYes

Fingerprint

Vascular Endothelial Growth Factor A
Endothelial Cells
Growth
Endothelium
Epithelium
Cell Proliferation
Vascular Endothelial Growth Factor Receptor
Gene Expression Profiling
Coculture Techniques
Protein Isoforms
Cytokines

Keywords

  • Airway
  • Basal cell
  • Cross-talk
  • Endothelium
  • Paracrine
  • VEGF-A

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Airway basal cell vascular endothelial growth factor-mediated cross-talk regulates endothelial cell-dependent growth support of human airway basal cells. / Curradi, Giacomo; Walters, Matthew S.; Ding, Bi Sen; Rafii, Shahin; Hackett, Neil R.; Crystal, Ronald.

In: Cellular and Molecular Life Sciences, Vol. 69, No. 13, 01.07.2012, p. 2217-2231.

Research output: Contribution to journalArticle

Curradi, Giacomo ; Walters, Matthew S. ; Ding, Bi Sen ; Rafii, Shahin ; Hackett, Neil R. ; Crystal, Ronald. / Airway basal cell vascular endothelial growth factor-mediated cross-talk regulates endothelial cell-dependent growth support of human airway basal cells. In: Cellular and Molecular Life Sciences. 2012 ; Vol. 69, No. 13. pp. 2217-2231.
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