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Bongkrekic acid alleviates airway inflammation via breaking the mPTP/mtDAMPs/RAGE feedback loop in a steroid-insensitive asthma model.
Chen, Ying; Huang, Junwen; Li, Yuemao; Chen, Yaoxin; Gong, Zhaoqian; Xu, Maosheng; Ma, Yanyan; Hu, Dapeng; Peng, Xianru; Xu, Guilin; Cai, Shaoxi; Liu, Laiyu; Zhao, Wenqu; Zhao, Haijin.
Afiliación
  • Chen Y; Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Huang J; Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Li Y; Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Chen Y; Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Gong Z; Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Xu M; Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Ma Y; Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Hu D; Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Peng X; Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Xu G; Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Cai S; Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Liu L; Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
  • Zhao W; Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: 398535173@qq.com.
  • Zhao H; Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address: zhjin@smu.edu.cn.
Biomed Pharmacother ; 177: 117111, 2024 Aug.
Article en En | MEDLINE | ID: mdl-39013220
ABSTRACT
Mitochondrial dysfunction is critical in the pathogenesis of asthma. Mitochondrial permeability transition pore (mPTP) regulates the release of mitochondrial damage-associated molecular patterns (mtDAMPs) to maintain mitochondrial homeostasis. Bongkrekic acid (BKA) is a highly selective inhibitor of mPTP opening, participates the progression of various diseases. This research investigated the exact roles of BKA and mPTP in the pathogenesis of asthma and elucidated its underlying mechanisms. In the present study, cytochrome c, one of the mtDAMPs, levels were elevated in asthmatic patients, and associated to airway inflammation and airway obstruction. BKA, the inhibitor of mPTP markedly reversed TDI-induced airway hyperresponsiveness, airway inflammation, and mitochondrial dysfunction. Pretreatment with mitochondrial precipitation, to simulate the release of mtDAMPs, further increased TDI-induced airway inflammation and the expression of RAGE in mice. Administration of the inhibitor of RAGE, FPS-ZM1, alleviated the airway inflammation, the abnormal open of mPTP and mitochondrial dysfunction induced by mtDAMPs and TDI. Furthermore, stimulation with different mtDAMPs activated RAGE signaling in human bronchial epithelial cells. Accordingly, our study indicated that mPTP was important and BKA was efficient in alleviating inflammation in TDI-induced asthma. A positive feedback loop involving mPTP, mtDAMPs and RAGE was present in TDI-induced asthma, indicating that mPTP might serve as a potential therapeutic target for asthma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Modelos Animales de Enfermedad / Poro de Transición de la Permeabilidad Mitocondrial Límite: Adult / Animals / Female / Humans / Male Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article Pais de publicación: Francia
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Modelos Animales de Enfermedad / Poro de Transición de la Permeabilidad Mitocondrial Límite: Adult / Animals / Female / Humans / Male Idioma: En Revista: Biomed Pharmacother Año: 2024 Tipo del documento: Article Pais de publicación: Francia