Chitosan promotes aquaporin formation and inhibits mucociliary differentiation of nasal epithelial cells through increased TGF-1 production

Although endoscopic sinus surgery is the mainstay surgical treatment for chronic rhinosinusitis, over 15% of patients require a repeat operation wherein postoperative adhesion formation is one of the main causes of failure. Several recently proposed chitosan-based biomaterials promote mucosal healing, reduce postoperative adhesion formation and restore mucociliary function of sinonasal mucosa. However, the effects of chitosan on cellular morphology, re-epithelization, and mucociliary differentiation of nasal epithelial cells (NECs) during the wound healing process have not been thoroughly investigated. The present study investigates the direct effects of chitosan on cellular growth, cellular migration, mucociliary differentiation and aquaporin (AQP) formation of NECs to elucidate the role of chitosan in sinonasal applications. Wound healing assay reveals that proliferation and migration of NECs are inhibited by incubation of chitosan. The NECs become irregular in shape without formation of tight junction and mucociliary differentiation of NECs is inhibited during a culture period with incubation of chitosan. However, AQP3 and AQP5 formation in NECs is significantly higher in chitosan groups than in control groups. Further, expressions of transforming growth factor (TGF)-1, Smad2, and Smad3 are significantly higher in the chitosan groups compared with controls. The results of the comparison indicate that chitosan inhibits proliferation, migration and mucociliary differentiation of NECs through increasing production of TGF-1. Copyright (c) 2016 John Wiley & Sons, Ltd.