Glial-derived neurotrophic factor promotes aberrant basal cell hyperplasia in nasal polyps
Clinical Immunology, 2025
Hou Y., Sun L., Su M., Yang W., Ji L., Zhou Y., Lu X., Yin N., Zhao J., Qiu Z., Wei Y., Wen W., Hu H.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Respiratory Diseases | Patient Stratification | Nasal Fluid |  Olink Target 96 |
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.