IGFBP3 and asthma: IGFBP-3 suppresses VEGF production by both IGF-1-dependent and hypoxia-inducible factor- (HIF-) dependent mechanisms, while VEGF has been shown to be associated with subepithelial fibrosis by regulation of TGF-β1 expression through the PI3K/AKT signaling pathway in asthma [213, 216].