2. Academic Validation
  3. Glial-derived neurotrophic factor promotes aberrant basal cell hyperplasia in nasal polyps

Glial-derived neurotrophic factor promotes aberrant basal cell hyperplasia in nasal polyps

  • Clin Immunol. 2025 Oct 14:281:110604. doi: 10.1016/j.clim.2025.110604.
Yilin Hou 1,  Lin Sun 2,  Mengqi Su 3,  Weiqiang Yang 4,  Lingchao Ji 4,  Yaqi Zhou 4,  Xiaochan Lu 4,  Na Yin 4,  Jiaqi Zhao 4,  Zihan Qiu 2,  Yi Wei 2,  Weiping Wen 2,  HongYi Hu 5
Affiliations

Affiliations

  • 1 Otorhinolaryngology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Guangdong province, China; Department of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, PR China; Department of Allergy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, PR China; Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, Guangdong, PR China; Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, PR China.
  • 2 Department of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, PR China; Department of Allergy, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, PR China; Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, Guangdong, PR China; Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou, Guangdong, PR China.
  • 3 Department of Cardiology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
  • 4 Otorhinolaryngology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Guangdong province, China.
  • 5 Otorhinolaryngology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Guangdong province, China. Electronic address: hyihu@sina.com.
PMID: 41075855 DOI: 10.1016/j.clim.2025.110604
Abstract

Background: Neurotrophins are elevated in nasal polyps (NPs) and/or allergies, exerting neurogenic inflammatory effects. Non-classical glial-derived neurotrophic factor (GDNF) family ligands (GFLs) remain poorly understood in chronic rhinosinusitis with NP (CRSwNP).

Methods: GDNF expression was analyzed in 67 nasal fluids (NFs) and 44 tissues via proteomic, transcriptomic, and immunohistochemical assays. Immunofluorescence co-staining identified GDNF and p63 + basal cells (BCs). Functional studies in human nasal epithelial cells (HNECs) assessed GDNF's affects on proliferation and barrier integrity. Bioinformatics identified regulatory networks and drug candidates.

Results: GDNF existed in NFs and tissues of CRSwNP, with higher abundance in eosinophilic NPs. P63 + BCs expression positively correlates with GDNF levels. GDNF potently activated MAPK/PI3K/Akt signaling in HNECs and induced Ki-67+/p63 + cells proliferation, while reduced distribution of claudin-1 at junctions. miR-204-5p/211-5p and two FDA-approved neuroactive drugs were predicted as GDNF modulators.

Conclusions: GDNF drives aberrant epithelial remodeling in CRSwNP via MAPK/PI3K signaling, highlighting its therapeutic potential for refractory disease.

Keywords

Glial-derived neurotrophic factor; Hyperplasia; MAPK/AKT signaling; Nasal basal cell; Nasal polyps.

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