Effect of nerve growth factor and keratinocyte growth factor on wound healing of the sinus mucosa

Abstract

The healing of the sinuses after sinus surgery is often compromised by the development of adhesions. The aim of this study was to determine whether nerve growth factor (NGF) and keratinocyte growth factor (KGF) aid epithelial and fibroblast wound healing after surgery. Two in vitro models were used to compare their effect on wound closure rates and expression of cell adhesion (E-cadherin), tight junction formation (zona occludens-1), cell proliferation (proliferative cell nuclear antigen and Ki67), and ciliogenesis (Foxj1 and beta tubulin IVb) genes by real-time reverse transcription polymerase chain reaction. Epithelial cells from sinonasal tissue were seeded in collagen-coated Transwells, creating an air-liquid interface, and a submergent model was used for fibroblasts. In epithelial cells, NGF (20-50 ng/mL) significantly decreased wound areas to <40% compared with controls that were still 70% of their original sizes by 24 hours (p<0.05). E-cadherin and zona occludens-1 expression were up-regulated by 20- and 2.5-fold, respectively, relative to controls. KGF (5-100 ng/mL) slowed fibroblast proliferation by reducing (0.8-fold) and Ki67 (0.25-fold) expression. NGF (10 ng/mL) slowed Ki67 expression by 0.5-fold. NGF accelerated in vitro epithelial wound closure while NGF and KGF reduced fibroblast proliferation.