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

IF 4.1 3区医学 Q2 IMMUNOLOGY

Clinical immunology Pub Date : 2025-12-01 Epub Date: 2025-10-10 DOI:10.1016/j.clim.2025.110604

Yilin Hou , Lin Sun , Mengqi Su , Weiqiang Yang , Lingchao Ji , Yaqi Zhou , Xiaochan Lu , Na Yin , Jiaqi Zhao , Zihan Qiu , Yi Wei , Weiping Wen , HongYi Hu

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引用次数: 0

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.

Abstract Image

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神经胶质源性神经营养因子促进鼻息肉异常基底细胞增生。

背景：神经营养因子在鼻息肉（NPs）和/或过敏中升高，发挥神经源性炎症作用。非经典神经胶质源性神经营养因子（GDNF）家族配体（GFLs）在慢性鼻窦炎伴NP （CRSwNP）中的作用尚不清楚。方法：通过蛋白质组学、转录组学和免疫组化分析67种鼻液（NFs）和44种组织中GDNF的表达。免疫荧光共染色鉴定GDNF和p63 + 基底细胞（BCs）。人鼻上皮细胞（HNECs）的功能研究评估了GDNF对增殖和屏障完整性的影响。生物信息学鉴定了监管网络和候选药物。结果：GDNF存在于CRSwNP的NFs和组织中，且在嗜酸性NPs中丰度较高。P63 + BCs表达与GDNF水平呈正相关。GDNF有效激活HNECs中MAPK/PI3K/Akt信号通路，诱导Ki-67+/p63 + 细胞增殖，同时减少连接处cludin -1的分布。预测miR-204-5p/211-5p和两种fda批准的神经活性药物可作为GDNF调节剂。结论：GDNF通过MAPK/PI3K信号驱动CRSwNP异常上皮重塑，突出了其治疗难治性疾病的潜力。

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来源期刊

Clinical immunology 医学-免疫学

CiteScore

12.30

自引率

1.20%

发文量

212

审稿时长

34 days

期刊介绍： Clinical Immunology publishes original research delving into the molecular and cellular foundations of immunological diseases. Additionally, the journal includes reviews covering timely subjects in basic immunology, along with case reports and letters to the editor.