The MEK1/2–ERK1/2 Pathway is Activated in Chronic Rhinosinusitis with Nasal Polyps

Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease that has a considerable impact on the quality of life. Alterations in signalling pathways may contribute to the ongoing inflammation and proliferation in CRSwNP. The MEK1/2-ERK1/2 pathway transmits signals from many extracellular molecules to regulate cellular processes. We examined tissue samples from nasal polyps and the inferior turbinate of patients with CRSwNP and the inferior turbinate from subjects with healthy mucosa. The expressions of MEK1/2, ERK1/2, and their active phosphorylated forms pMEK1/2 and pERK1/2 were analysed using DNA microarray, quantitative real-time PCR, protein array, Western hybridisation, and immunohistochemistry. We detected increased MEK1/2 protein expression in nasal polyps compared to the inferior turbinates of patients with CRSwNP or healthy mucosa. We also found a higher amount of MEK1/2 in the inferior turbinates of patients with CRSwNP compared to those with healthy mucosa. Most importantly, we observed a significant increase in the phosphorylation of MEK1/2 and ERK1/2 in nasal polyps compared to both types of controls. We observed activation of the MEK1/2-ERK1/2 pathway in nasal polyps. Interestingly, we did not see the same activation pattern in different tiers of the MEK1/2-ERK1/2 signalling cascade. One explanation for this result is that the components enhance the complex MEK-ERK cascade in a distinct manner, enabling a wide variety of functions. The MEK1/2-ERK1/2 pathway appears to play a pivotal role in the pathogenesis of CRSwNP.

Potential Involvement of the Epidermal Growth Factor Receptor Ligand Epiregulin and Matrix Metalloproteinase-1 in Pathogenesis of Chronic Rhinosinusitis

“…If this hypothesis is correct, one would expect to observe EGFR-related transcription factors to be activated in CRS tissue. Accordingly, Linke and colleagues (48) reported that the ERK1/2 pathway was activated in tissue from patients with CRSwNP. Based on the present findings, EREG is the most likely stimulus of this activation in vivo.…”

Effects of Erythromycin on the Proliferation and Apoptosis of Cultured Nasal Polyp-Derived Cells and the Extracellular Signal-Regulated Kinase (ERK)/Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway

“…Recent studies have shown that interleukin (IL)-1β regulates the expression of glucocorticoid receptor isoforms in nasal polyps in vitro via p38 MAPK and JNK signal transduction pathways, supporting the role of MAPK in the development of nasal polyps [ 25 ]. Another study has shown that overexpression of the ERK/MAPK pathway is closely related to the occurrence and development of nasal polyps [ 9 ]. The findings of the present study showed that the levels of p-ERK and p-MEK in nasal polyp tissue-derived cells were elevated, indicating activation od the ERK/MAPK signaling pathway.…”

“…The extracellular signal-regulated kinase (ERK) and mitogen-activated protein kinase (MAPK) signaling pathway can activate a variety of nuclear transcription factors and participate in multiple intracellular protein kinase reactions to regulate the transcription and expression of related target genes, which affect cell biology, proliferation, apoptosis, inflammatory response, and other biological processes [ 7 , 8 ]. It has been shown that the expression or functional activity of key proteins in the ERK/MAPK pathway were increased in nasal polyps, suggesting that overexpression of components of the ERK/MAPK signaling pathway has a role in the pathogenesis of nasal polyps [ 9 ].…”

Nasal Polyposis: Insights in Epithelial-mesenchymal Transition and Differentiation of Polyp Mesenchymal Stem Cells

“…The MEK1/2-ERK1/2 pathway is activated in CRSwNP [43]. There was an induction of the amount of MEK1/2 and phosphorylation of MEK1/2 and ERK1/2 in nasal polyps compared to healthy nasal mucosa.…”