Vollständiger Abstract
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Abstract Although diabetic complications are well-established in multiple organs, their impact on the respiratory system remains unclear. Clinical evidence indicates accelerated chronic obstructive pulmonary disease (COPD) progression in individuals with diabetes, yet the underlying mechanisms are poorly defined. Using single-cell RNA sequencing of airway epithelium, we identified distinct transcriptional alterations in COPD patients with or without diabetes, particularly in host–defense pathways related to viral infection, which is a key driver of COPD exacerbations. Functionally, hyperglycemia enhanced influenza virus susceptibility in both COPD-derived epithelial cells and COPD mice with diabetes, indicating compromised airway defense. We further demonstrated that hyperglycemia promotes advanced glycation end products (AGEs) accumulation in airway epithelium, with AGEs levels correlating with infection severity. Pharmacological inhibition of AGEs formation with aminoguanidine significantly reduced viral load both in vitro and in vivo. Mechanistically, AGEs activate p38/ERK/IKK proinflammatory signaling via RAGE and MD2 receptors, leading to epithelial injury and heightened viral susceptibility. Our findings reveal a hyperglycemia-AGEs-RAGE/MD2 axis that increases viral susceptibility in COPD, highlighting AGEs targeting as a promising therapeutic strategy for COPD patients with diabetes.
Bibliografischer Nachweis
Publikationsdaten
- Autor:innen
- Zhenfeng Chen, Yueying Qin, Bingqi Lin, Linle Jiang, Zhencheng Feng, Shiying Chen, Zuodong Ye, Min Zhou, Jia Li, De Yun Wang, Nanshan Zhong, Panpan Hou, Ziqing Zhou, Lei Wang, Yang Peng
- Quelle
- EMBO Molecular Medicine
- Publikation
- 2026-08-17
- Band / Ausgabe
- Nicht angegeben
- Seiten
- Nicht angegeben
- ISSN / ISBN
- 1757-4684
- Zitationen
- 1 laut Crossref
- Referenzen
- 75 hinterlegt
Zitieren
Zitierfähiger Nachweis
Zhenfeng Chen, Yueying Qin, Bingqi Lin, Linle Jiang, Zhencheng Feng, Shiying Chen, Zuodong Ye, Min Zhou, Jia Li, De Yun Wang, Nanshan Zhong, Panpan Hou, Ziqing Zhou, Lei Wang, Yang Peng (2026). Blocking AGEs reduces airway epithelial viral susceptibility in diabetes-exacerbated COPD. EMBO Molecular Medicine. https://doi.org/10.1038/s44321-026-00502-9
Kontext
Themen, Förderung und Nutzung
Förderung: National Natural Science Foundation of China, R&D Program of Guangzhou Laboratory, grant of State Key Laboratory of Respiratory Disease, National Natural Science Foundation - Outstanding Youth Fund, Youth program of Guangzhou National Laboratory, National Key Research and Development Program of China, Noncommunicable Chronic Diseases - National Science and Technology Major Project, Guangzhou Municipal Science and Technology Bureau, Guangzhou Key Research and Development Program, Guangzhou Science and Technology Project, Major Project of Guangzhou National Laboratory Grant, Pearl River Talent Recruitment Program
Lizenzhinweise: Lizenz 1