2. Academic Validation
  3. Hypoxia disrupts the nasal epithelial barrier by inhibiting PTPN2 in chronic rhinosinusitis with nasal polyps

Hypoxia disrupts the nasal epithelial barrier by inhibiting PTPN2 in chronic rhinosinusitis with nasal polyps

  • Int Immunopharmacol. 2023 Mar 22;118:110054. doi: 10.1016/j.intimp.2023.110054.
Meiping Zhang 1,  Yishan Xiong 1,  Junhao Tu 1,  Binxiang Tang 1,  Zhiqiang Zhang 1,  Jieqing Yu 2,  Li Shen 1,  Qing Luo 1,  Jing Ye 3
Affiliations

Affiliations

  • 1 Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
  • 2 Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China; Institute of Jiangxi Otorhinolaryngology Head & Neck Surgery, Nanchang, Jiangxi Province, China.
  • 3 Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China; Institute of Jiangxi Otorhinolaryngology Head & Neck Surgery, Nanchang, Jiangxi Province, China. Electronic address: [email protected].
PMID: 36963262 DOI: 10.1016/j.intimp.2023.110054
Abstract

Background: Hypoxia is involved in inflammation and immune response; however, its role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) is not fully understood. We aimed to investigate the mechanisms by which hypoxia disrupts the nasal epithelial barrier in CRSwNP.

Methods: The expression of hypoxia-inducible factor-1α (HIF-1α), protein tyrosine Phosphatase non-receptor type 2 (PTPN2), and tight junction (TJ) components (claudin-4, occludin, and ZO-1) was detected in nasal polyps using immunohistochemistry, western blotting, and qRT-PCR. Primary human nasal epithelial cells (HNECs), BEAS-2B cells, and an eosinophilic CRSwNP (Eos CRSwNP) mouse model were used to explore the potential mechanisms by which hypoxia disrupts the nasal epithelial barrier.

Results: HIF-1α expression in the non-Eos and Eos CRSwNP groups was higher than in the control group, and the expression of PTPN2 and TJs in the non-Eos and Eos CRSwNP groups were lower than those in the control group. Hypoxia decreased the expression of PTPN2 and TJs and increased epithelial cell permeability in HNECs, which was blocked by the HIF-1α inhibitor PX-478. PTPN2 overexpression inhibited hypoxia-induced downregulation of TJ expression in BEAS-2B cells, whereas PTPN2-knockdown aggravated the effects of hypoxia. In the Eos CRSwNP mouse model, both PX-478 and PTPN2 overexpression reduced the formation of nasal polypoid lesions, permeability of the nasal epithelium, and restored TJ expression.

Conclusions: Our data indicate that hypoxia-induced HIF-1α downregulates TJ expression by inhibiting PTPN2, thereby disrupting the nasal epithelial barrier and promoting CRSwNP development. HIF-1α and PTPN2 may be potential targets for the treatment of CRSwNP.

Keywords

Chronic rhinosinusitis with nasal polyps; Hypoxia-inducible factor-1α; Nasal epithelial barrier; Protein tyrosine phosphatase non-receptor type 2; Tight junctions.

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