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SLC27A2标记慢性鼻-鼻窦炎伴鼻息肉中由2型炎症驱动的鼻上皮细胞脂质过氧化。

SLC27A2 marks lipid peroxidation in nasal epithelial cells driven by type 2 inflammation in chronic rhinosinusitis with nasal polyps.

作者信息

Park Jaewoo, Jang Jung Yeon, Kim Jeong Heon, Yi Se Eun, Lee Yeong Ju, Yu Myeong Sang, Chung Yoo-Sam, Jang Yong Ju, Kim Ji Heui, Kang Kyuho

机构信息

Department of Biological Sciences and Biotechnology, Chungbuk National University, Cheongju, Republic of Korea.

Department of Otorhinolaryngology-Head and Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

出版信息

Exp Mol Med. 2025 Apr;57(4):856-871. doi: 10.1038/s12276-025-01440-1. Epub 2025 Apr 7.

DOI:10.1038/s12276-025-01440-1
PMID:40195539
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12045986/
Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by persistent inflammation and epithelial cell dysfunction, but the underlying molecular mechanisms remain poorly understood. Here we show that dysregulated lipid metabolism and increased lipid peroxidation in nasal polyp epithelial cells contribute to the pathogenesis of CRSwNP. Integrated analysis of bulk and single-cell RNA sequencing data reveals upregulation of SLC27A2/FATP2 in nasal polyp epithelium, which correlates with increased lipid peroxidation. SLC27A2-positive epithelial cells exhibit enriched expression of lipid peroxidation pathway genes and enhanced responsiveness to IL-4/IL-13 signaling from Th2 and ILC2 cells. Inhibition of IL-4/IL-13 signaling by dupilumab reduces expression of lipid peroxidation-associated genes, including SLC27A2. In eosinophilic CRSwNP, SLC27A2 expression correlates with disease severity. Pharmacological inhibition of FATP2 in air-liquid interface cultures of nasal epithelial cells decreases expression of IL13RA1 and lipid peroxidation-related genes. Our findings identify FATP2-mediated lipid peroxidation as a key driver of epithelial dysfunction and inflammation in CRSwNP, providing new insights into disease mechanisms and potential therapeutic targets.

摘要

伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）的特征是持续炎症和上皮细胞功能障碍，但其潜在的分子机制仍知之甚少。在此我们表明，鼻息肉上皮细胞中脂质代谢失调和脂质过氧化增加促成了CRSwNP的发病机制。对批量和单细胞RNA测序数据的综合分析揭示了鼻息肉上皮中SLC27A2/FATP2的上调，这与脂质过氧化增加相关。SLC27A2阳性上皮细胞表现出脂质过氧化途径基因的富集表达以及对来自Th2和ILC2细胞的IL-4/IL-13信号增强的反应性。度普利尤单抗对IL-4/IL-13信号的抑制降低了包括SLC27A2在内的脂质过氧化相关基因的表达。在嗜酸性CRSwNP中，SLC27A2表达与疾病严重程度相关。在鼻上皮细胞的气液界面培养物中对FATP2进行药理学抑制可降低IL13RA1和脂质过氧化相关基因的表达。我们的研究结果确定FATP2介导的脂质过氧化是CRSwNP中上皮功能障碍和炎症的关键驱动因素，为疾病机制和潜在治疗靶点提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0f/12045986/ae96721492c5/12276_2025_1440_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0f/12045986/36a51b31cebf/12276_2025_1440_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0f/12045986/c1939909353e/12276_2025_1440_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0f/12045986/c137bb4e0284/12276_2025_1440_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0f/12045986/793ed180acfb/12276_2025_1440_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0f/12045986/575963f4de41/12276_2025_1440_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0f/12045986/ae96721492c5/12276_2025_1440_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0f/12045986/36a51b31cebf/12276_2025_1440_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0f/12045986/c1939909353e/12276_2025_1440_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0f/12045986/c137bb4e0284/12276_2025_1440_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0f/12045986/793ed180acfb/12276_2025_1440_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0f/12045986/575963f4de41/12276_2025_1440_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f0f/12045986/ae96721492c5/12276_2025_1440_Fig7_HTML.jpg

相似文献

[1]
SLC27A2 marks lipid peroxidation in nasal epithelial cells driven by type 2 inflammation in chronic rhinosinusitis with nasal polyps.

Exp Mol Med. 2025-4

[2]
Chronic rhinosinusitis with nasal polyps is associated with impaired TMEM16A-mediated epithelial chloride secretion.

J Allergy Clin Immunol. 2021-6

[3]
Increased SERPINB2 potentiates 15LO1 expression via STAT6 signalling in epithelial cells in eosinophilic chronic rhinosinusitis with nasal polyps.

Clin Exp Allergy. 2024-6

[4]
Role of IFN-γ, IL-13, and IL-17 on mucociliary differentiation of nasal epithelial cells in chronic rhinosinusitis with nasal polyps.

Clin Exp Allergy. 2016-3

[5]
Notch-1 signaling activation sustains overexpression of interleukin 33 in the epithelium of nasal polyps.

J Cell Physiol. 2018-9-27

[6]
FERMT1 contributes to the epithelial-mesenchymal transition of chronic rhinosinusitis with nasal polyps via PI3K/Akt signaling.

Int Immunopharmacol. 2024-12-25

[7]
Neutrophils in nasal polyps exhibit transcriptional adaptation and proinflammatory roles that depend on local polyp milieu.

JCI Insight. 2024-11-22

[8]
Matrix metalloproteinase-12 by M2 macrophages induced epithelial to mesenchymal transition in chronic rhinosinusitis with nasal polyps.

PLoS One. 2024-12-31

[9]
Epithelial activators of type 2 inflammation: Elevation of thymic stromal lymphopoietin, but not IL-25 or IL-33, in chronic rhinosinusitis with nasal polyps in Chicago, Illinois.

Allergy. 2018-11

[10]
Tc17/IL-17A Up-Regulated the Expression of MMP-9 via NF-κB Pathway in Nasal Epithelial Cells of Patients With Chronic Rhinosinusitis.

Front Immunol. 2018-9-19

本文引用的文献

[1]
Rhinovirus infection of airway epithelial cells uncovers the non-ciliated subset as a likely driver of genetic risk to childhood-onset asthma.

Cell Genom. 2024-9-11

[2]
Identification of hub genes associated with neutrophils in chronic rhinosinusitis with nasal polyps.

Sci Rep. 2024-8-27

[3]
FATP2 activates PI3K/Akt/mTOR pathway by inhibiting ATF3 and promotes the occurrence and development of bladder cancer.

Cell Signal. 2024-5

[4]
Bulk and single-cell transcriptome sequencing reveal the metabolic feature in chronic rhinosinusitis with polyps.

Clin Exp Allergy. 2024-1

[5]
Perturbated glucose metabolism augments epithelial cell proinflammatory function in chronic rhinosinusitis.

J Allergy Clin Immunol. 2023-4

[6]
Ferroptotic mechanisms and therapeutic targeting of iron metabolism and lipid peroxidation in the kidney.

Nat Rev Nephrol. 2023-5

[7]
IL-13-associated epithelial remodeling correlates with clinical severity in nasal polyposis.

J Allergy Clin Immunol. 2023-5

[8]
Oxidative Stress and Antioxidants in Chronic Rhinosinusitis with Nasal Polyps.

Antioxidants (Basel). 2023-1-14

[9]
Improving diagnosis of mitochondrial fatty-acid oxidation disorders.

Eur J Hum Genet. 2023-3

[10]
Transcriptomic Analysis of Genes Associated with Oxidative Stress in Chronic Rhinosinusitis Patients with Nasal Polyps: Identifying Novel Genes Involved in Nasal Polyposis.

Antioxidants (Basel). 2022-9-25

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