Fibroblast growth factor-7 promotes repair of primary human bronchial epithelial cells

Fibroblast growth factor 7 (FGF7) is a potent and specific epithelial mitogen that can modulate alveolar repair however, the impact on human bronchial epithelial cells (hBECs) is limited. This study characterised repair responses of hBECs from healthy and fibrotic lungs to exogenous FGF7 supplementation. When healthy hBECs were cultured under a physiological stressor of low seeding density, treatment with recombinant human FGF7 (rhFGF7) reduced cytotoxicity, and increased survival and proliferation. Cell migration was assessed using a scratch assay, where pre-treatment of hBECs with rhFGF7 significantly increased wound closure (50.5%, p<0.001) compared to control (15.3%), accompanied by upregulation of FGF signalling genes including mTOR, PIK3CA and MAPK3. To explore modified mRNA as an alternative protein supplementation strategy for wound repair, it was found that hBECs were able to secrete dose responsive levels of FGF7 following mRNA transfection (modFGF7), and when applied to a monolayer of hBECs, wound closure was significantly improved compared to control (36.1%, p<0.05). In contrast, when hBECs from idiopathic pulmonary fibrosis (IPF) donors were cultured at low density or injured by scratch, untreated cells were capable of notable survival and wound closure (27.1%) that was not improved by rhFGF7 or modFGF7 treatment. It was found that baseline expression of genes associated with proliferation and survival including PIK3CA, AKT1 and MTOR was higher in IPF hBEC. This study demonstrates a role of FGF7 in proliferation, survival and migration of healthy hBECs but requires careful assessment dependant on disease context.