The RNA-binding protein Mex3B regulates airway remodeling through modulation of TGFBR3 mRNA stability in chronic rhinosinusitis.

Abstract Objective: To explore the pathogenic function of Mex3 RNA binding family member B (Mex3b) in chronic rhinosinusitis(CRS). Methods: The expression of Mex3b, TGF-β receptor III (TGFBR3), TGF-β2, p-Smad2 were studied by quantitative RT-PCR, immunohistochemistry, western blotting, and ELISA. The binding of MEX3b with TGFBR3was test by improved RNA immunoprecipitation–coupled high-throughput sequencing (iRIP-Seq). Results: Compared to control subjects, mNRA and protein expression of Mex3b in nasal epithelial cells from CRSwNP patients are upregulated. And Mex3b mRNA and protein levels in cultured human nasal epithelial cells(HNECs) obtained from control subjects were upregulated by LPS, CpG and IL-1β. Incresed Mex3b downregulates TGFBR3expression in airway epithelial cells by binding to TGFBR3mRNA, which results in downregulated level of TGFBR3in CRS compared to control subjects. Loss of TGFBR3 inhibits TGF-β2 induced gene transcription in nasal epithelial cells. And Mex3b suppresses TGF-β2 signaling activation by downregulating TGFBR3 expression in nasal epithelial cells. Mex3b and TGFBR3 expression levels are correlated with tissue edema in CRSwNP. Conclusions: The upregulation of Mex3b in CRSwNP suppresses TGF-β2 signaling activation by downregulating TGFBR3 expression in nasal epithelial cells, and thefore regulates tissue remodeling of CRS.