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Author Spotlight: Investigating the Pathophysiology of Eosinophilic Esophagitis
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Oncostatin M promotes epithelial barrier dysfunction in patients with eosinophilic chronic rhinosinusitis with nasal

Bao-Feng Wang1, Ying-Ying Wang1, Hai Lin2

  • 1Department of Otolaryngology-Head and Neck Surgery, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, P.R. China.

Tissue Barriers
|September 3, 2024
PubMed
Abstract

Insights

Oncostatin M (OSM) elevates matrix metalloproteinases (MMP)-1 and -7 in nasal cells, contributing to barrier dysfunction in eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP). This highlights OSM

Area of Science:

  • Immunology
  • Cell Biology
  • Otorhinolaryngology

Background:

  • Eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP) is associated with mucosal epithelial barrier dysfunction.
  • Oncostatin M (OSM) is implicated in promoting this dysfunction by inducing matrix metalloproteinases (MMPs).

Purpose of the Study:

  • To investigate the role and mechanisms of OSM in regulating MMP-1 and MMP-7 synthesis in nasal epithelial cells (NECs).
  • To assess the impact of OSM on the epithelial barrier in the context of Eos CRSwNP.

Main Methods:

  • Quantitative polymerase chain reaction (qPCR), immunofluorescence, and immunohistochemistry were used to assess OSM, OSMR, MMP-1, and MMP-7 expression in nasal tissues and NECs.
  • Primary NECs and air-liquid interface (ALI) cultures were stimulated with OSM and cytokines.
  • ELISA and immunofluorescence were employed to measure protein expression and tight junction protein (occludin) localization.

Main Results:

  • Elevated OSMRβ, MMP-1, and MMP-7 levels were observed in Eos CRSwNP tissues and NECs compared to controls.
  • OSM stimulation significantly increased MMP-1 and MMP-7 expression in NECs, which was inhibited by STAT3 and PI3K inhibitors.
  • OSM stimulation disrupted occludin localization in NECs, indicating compromised tight junctions, an effect reversed by a pan-MMP inhibitor.

Conclusions:

  • OSM induces the synthesis and release of MMP-1 and MMP-7 in NECs.
  • MMP-1 and MMP-7 play a crucial role in the mucosal epithelial barrier dysfunction observed in Eos CRSwNP patients.
  • Targeting OSM or MMPs may offer therapeutic strategies for Eos CRSwNP.
Keywords:
MMP-1MMP-7OSMOSMRβeosinophilic chronic rhinosinusitis with nasal polypsnasal epithelial cellsoccludin

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