The role of MAPK signaling pathway in the repair of mucosal epithelium in chronic sinusitis with nasal polyps and without nasal polyps

: Objective:To evaluate the differences between CRS and normal subjects and between chronic rhinosinusitis without nasal polys(CRSsNP) and chronic rhinosinusitis with nasal polys(CRSwNP) in the regulation of EGF pathways and the regulating proliferative position of MAPK pathways.Method: We evaluated the proliferation rates of ethmoidal mucosal cells before and after stimulation with EGF,epidermal growth factor receptor(EGFR) kinase inhibitor AG1478, and extracellular signalregulated kinase1/2(ERK1/2) inhibitorPD98059 using MTT assays.We also analyzed the sinonasal epithelial cells collected from control subjects and patients with CRS subtypes CRSsNP and CRSwNP for the expression of ERK1/2,phosphorylated ERK1/2 using western blot analyses.Result:The proliferation rates of sinonasal epithelial cells before and after EGF stimulation were lower in CRS patients than in the controls.AG1478 or PD98059 inhibitor treatment of control epithelial cells did not result in a significant difference in proliferation.Although,AG1478 and PD98059 inhibited the proliferation of CRS cells, the level of proliferation inhibition was markedly different in CRSsNP.AG1478 suppressed the proliferation of CRSwNP epithelial cells, whereas PD98059 had no effect.The ratio of ERK1/2 phosphorylation in CRS cells was lower than that of the control cells.Conclusion:MAPK classical pathway and other pathways might be active at the same time to stimulate epithelial cell proliferation in CRSsNP. When the classical pathway was blocked in CRSwNP, some other pathway could have completely compensated the proliferation.