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FGF10 protects against LPS-induced epithelial barrier injury and inflammation by inhibiting SIRT1-ferroptosis pathway in acute lung injury in mice.
Lin, Lidan; Yang, Li; Wang, Nan; Chen, Siyue; Du, Xiaotong; Chen, Ran; Zhang, Hongyu; Kong, Xiaoxia.
Afiliación
  • Lin L; School of Basic Medical Sciences, Institute of Hypoxia Research, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • Yang L; Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • Wang N; School of Basic Medical Sciences, Institute of Hypoxia Research, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • Chen S; Department of Children's Respiration disease, the Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325000, Zhejiang, China.
  • Du X; School of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang 315302, China.
  • Chen R; School of Basic Medical Sciences, Institute of Hypoxia Research, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
  • Zhang H; School of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang 315302, China; Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang 315302, China; Department of Pharmacy, Zhuji People's Hospital, Wenzhou Medical University, Zhuji, Shaoxing, Zhejiang, 311800, China.
  • Kong X; School of Basic Medical Sciences, Institute of Hypoxia Research, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China; Cixi Biomedical Research Institute, Wenzhou Medical University, Zhejiang 315302, China. Electronic address: kongxx@wmu.edu.cn.
Int Immunopharmacol ; 127: 111426, 2024 Jan 25.
Article en En | MEDLINE | ID: mdl-38147776
ABSTRACT
Pulmonary alveolar epithelial cell injury is considered the main pathological and physiological change in acute lung injury. Ferroptosis in alveolar epithelial cells is one of crucial factors contributing to acute lung injury (ALI). Therefore, reducing ferroptosis and repair epithelial barrier is very necessary. More and more evidence suggested that FGF10 plays an important role in lung development and repair after injury. However, the relationship between FGF10 and ferroptosis remains unclear. This study aims to explore the regulatory role of FGF10 on ferroptosis in ALI. Differential gene expression analysis indicated that genes associated with ferroptosis showed that FGF10 can significantly alleviate LPS induced lung injury and epithelial barrier damage by decreasing levels of malonaldehyde(MDA), and lipid ROS. SIRT1 activator (Resveratrol) and inhibitor (EX527) are used in vivo showed that FGF10 protects ferroptosis of pulmonary epithelial cells through SIRT1 signal. Furthermore, knockdown of FGFR2 gene reduced the protective effect of FGF10 on acute lung injury in mice and SIRT1 activation. After the application of NRF2 inhibitor ML385 in vitro, the results showed that SIRT1 regulated the expression of ferroptosis related proteins NRF2, GPX4 and FTH1 are related to activation of NRF2. These data indicate that SIRT-ferroptosis was one of the critical mechanisms contributing to LPS-induced ALI. FGF10 is promising as a therapeutic candidate against ALI through inhibiting ferroptosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lesión Pulmonar Aguda / Ferroptosis Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Lesión Pulmonar Aguda / Ferroptosis Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Países Bajos