Hyaluronan antagonizes the differentiation effect of TGF-β1 on nasal epithelial cells through down-regulation of TGF-β type I receptor

Abstract

Although hyaluronan (HA)-based biomaterials have been proposed to promote mucociliary differentiation of nasal epithelial cells (NECs), the mechanism by which HA affects the growth and differentiation of NECs has not been thoroughly explored. This study investigates the effect and mechanism of HA on the differentiation of NECs. The experiment cultures human NECs in four conditions, namely controls, transforming growth factor (TGF)-β1, TGF-β1 + HA and HA groups. In the TGF group, the NECs become irregular shape without formation of tight junction and mucociliary differentiation of NECs is inhibited. Epithelial–mesenchymal transition (EMT) of NECs also occurs in the TGF group. However, with addition of HA in TGF groups, NECs reveal the mucociliary phenotypes of epithelial cells with tight junction expression. Incubation of TGF-β1 in an NEC culture leads to an increase in phosphorylated type 1 TGF-β receptors (p-TβRI). This increase is attenuated when NECs are cultured in the presence of HA. Similar expressions are observed in phosphorylated smad2/smad3. Additionally, HA-dependent inhibition of TGF-β1 signalling is inhibited by co-incubation with a blocking antibody to CD44. Experimental results indicate that HA can antagonize TGF-β1 effect on EMT and mucociliary differentiation of NECs by down-regulation of TβR I, which is via CD44.