fibroblast growth factor 2 augments transforming growth factor beta 1 induced epithelial-mesenchymal transition in lung cell culture model

Impaired lung epithelial cell regeneration following injury may contribute to thedevelopment of pulmonary fibrosis. epithelial-mesenchymal transition (emt) is a criticalevent in embryonic development, wound healing following injury, and even cancerprogression. previous studies have shown that the combination of transforming growthfactor beta-1 (tgfβ1) and fibroblast growth factor 2 (fgf2) induces emt during cancermetastasis. however, this synergy remains to be elucidated in inducing emt associated withwound healing after injury. we set out this study to determine the effect of fibroblast growthfactor 2 (fgf2) on tgfβ1-induced emt in the human lung epithelium.beas-2b and a549 cells were treated with tgfβ1, fgf2, or both. emt phenotype wasinvestigated morphologically and by measuring mrna expression levels; using quantitativereal-time pcr. e-cadherin expression was assayed by western blot and immunofluorescencestaining. cell migration was confirmed using a wound-healing assay.tgfβ1 induced a morphological change and a significant increase in cell migration ofbeas-2b cells. tgfβ1 significantly reduced e-cadherin (cdh1) mrna expression andmarkedly induced expression of n-cadherin (cdh2), tenascin c (tnc), fibronectin (fn),actin alpha 2 (acta2), and collagen i (col1a1). while fgf2 alone did not significantlyalter emt gene expression, it enhanced tgfβ1-induced suppression of cdh1 andupregulation of acta2, but not tnc, fn, and cdh2. fgf2 significantly inhibitedtgfβ1-induced col1a1 expression. furthermore, fgf2 maintained tgfβ1-inducedmorphologic changes and increased the migration of tgfβ1-treated cells.this study suggests a synergistic effect between tgfβ1 and fgf2 in inducing emt in lungepithelial cells, which may play an important role in wound healing and tissue repair after injury.