Eupatilin alleviates inflammation and epithelial-to-mesenchymal transition in chronic rhinosinusitis with nasal polyps by upregulating TFF1 and inhibiting the Wnt/β-catenin signaling pathway.

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease characterized by high prevalence and morbidity. However, its pathogenesis is still obscure. This work focuses on the effects of Eupatilin (EUP) on inflammation reaction and the epithelial-to-mesenchymal transition (EMT) process in CRSwNP. In vivo and in vitro CRSwNP models were established based on BALB/c mice and human nasal epithelial cells (hNECs) to investigate the effects of EUP on EMT and inflammation in CRSwNP. Protein levels of TFF1, EMT-related factors (E-cadherin, N-cadherin, and Vimentin), and Wnt/β-catenin signaling-related proteins (Wnt3α and β-catenin) were assayed via western blotting. Pro-inflammatory factors (TNF-α, IL-6, and IL-8) were assessed via ELISA assay. EUP treatment significantly reduced the number of polyps, epithelial thickness, and mucosal thickness in CRSwNP mice. Besides, EUP treatment also suppressed inflammation reaction and EMT events in CRSwNP mice and SEB-challenged hNECs in a dose-dependent manner. Also, EUP treatment dose-dependently upregulated TFF1 expression and inhibited Wnt/β-catenin activation in CRSwNP mice and SEB-challenged hNECs. In addition, TFF1 inhibition or Wnt/β-catenin activation partially abated EUP-mediated protection against SEB-induced inflammation reaction and EMT events in hNECs. Taken together, our findings highlighted the inhibitory role of EUP on the inflammation and EMT processes in CRSwNP in vivo and in vitro via upregulating TFF1 and inhibiting the Wnt/β-catenin signaling, suggesting EUP could be a promising therapeutic agent for CRSwNP.