The human airway epithelium is a pseudostratified heterogenous layer comprised of cili-ated, secretory, intermediate and basal cells. As the stem/progenitor population of the airway epi-thelium, 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 3 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 ex-press 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 endothe-lium, the purpose of which is to modulate endothelial activation and in turn stimulate and sustain basal cell growth. / I risultati preliminari dello studio suggeriscono che il vascular endothelial growth factor A(VEGFA) e’ attivamente secreto dalle cellule basali dell’epitelio bronchiale e svolge una funzione paracrina nell’attivazione della cascata delle mitogen-activated protein kinases (MAPKs) nelle cellule endoteliali mediata dal VEGF receptor type 2. Utilizzando un sistema di co-coltura di cellule basali primarie delle vie aeree umane con cellule endoteliali umane, abbiamo mostrato come il VEGFA secreto dalle cellule basali sia in grado di attivare le cellule endoteliale che a loro volta, esprimono mediatori capaci di stimolare e sostenere la proliferazione delle cellule basali stesse. Questi dati dimostrano un cross-talk mediato dal rilascio di VEGFA tra le cellule basali dell’epitelio bronchiale e l’endotelio, il cui scopo è di modulare l'attivazione endoteliale e, a sua volta stimolare e sostenere la crescita delle cellule basali.
| Identifer | oai:union.ndltd.org:unibo.it/oai:amsdottorato.cib.unibo.it:5925 |
| Date | 15 April 2013 |
| Creators | Curradi, Giacomo <1977> |
| Contributors | Saltini, Cesare |
| Publisher | Alma Mater Studiorum - Università di Bologna |
| Source Sets | Università di Bologna |
| Language | English |
| Detected Language | English |
| Type | Doctoral Thesis, PeerReviewed |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
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