Fibroblast growth factor 10 alleviates acute lung injury by inhibiting excessive autophagy via Nrf2

in Journal of Endocrinology
Authors:
Shuai Huang Zhejiang Provincial Key Laboratory of Interventional Pulmonology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Yincong Xue Zhejiang Provincial Key Laboratory of Interventional Pulmonology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Wanying Chen Department of Psychiatry, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Mei Xue Central Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Lei Miao Department of Gastroenterology and Hepatology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Li Dong Zhejiang Provincial Key Laboratory of Interventional Pulmonology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Hao Zuo Zhejiang Provincial Key Laboratory of Interventional Pulmonology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Hezhi Wen Zhejiang Provincial Key Laboratory of Interventional Pulmonology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Xiong Lei Zhejiang Provincial Key Laboratory of Interventional Pulmonology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Zhixiao Xu Zhejiang Provincial Key Laboratory of Interventional Pulmonology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Meiyu Quan Zhejiang Provincial Key Laboratory of Interventional Pulmonology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Lisha Guo Zhejiang Provincial Key Laboratory of Interventional Pulmonology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Yawen Zheng Zhejiang Provincial Key Laboratory of Interventional Pulmonology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Zhendong Wang Zhejiang Provincial Key Laboratory of Interventional Pulmonology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Li Yang Zhejiang Provincial Key Laboratory of Interventional Pulmonology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Yuping Li Zhejiang Provincial Key Laboratory of Interventional Pulmonology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

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Chengshui Chen Zhejiang Provincial Key Laboratory of Interventional Pulmonology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
Department of Pulmonary and Critical Care Medicine, the Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, China

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https://orcid.org/0000-0003-4841-9911

Correspondence should be addressed to L Yang or Y Li or C Chen: taiyang2630@163.com or wzliyp@163.com or chenchengshui@wmu.edu.cn

*(S Huang, Y Xue and W Chen contributed equally to this work)

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Acute lung injury (ALI) is associated with an increased incidence of respiratory diseases, which are devastating clinical disorders with high global mortality and morbidity. Evidence confirms that fibroblast growth factors (FGFs) play key roles in mediating ALI. Mice were treated with LPS (lipopolysaccharide: 5 mg/kg, intratracheally) to establish an in vivo ALI model. Human lung epithelial BEAS-2B cells cultured in a corresponding medium with LPS were used to mimic the ALI model in vitro. In this study, we characterized FGF10 pretreatment (5 mg/kg, intratracheally) which improved LPS-induced ALI, including histopathological changes, and reduced pulmonary edema. At the cellular level, FGF10 pretreatment (10 ng/mL) alleviated LPS-induced ALI accompanied by reduced reactive oxygen species (ROS) accumulation and inflammatory responses, such as IL-1β, IL-6, and IL-10, as well as suppressed excessive autophagy. Additionally, immunoblotting and co-immunoprecipitation showed that FGF10 activated nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway via Nrf2 nuclear translocation by promoting the interaction between p62 and keap1, thereby preventing LPS-induced ALI. Nrf2 knockout significantly reversed these protective effects of FGF10. Together, FGF10 protects against LPS-induced ALI by restraining autophagy via p62-Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 signaling pathway, implying that FGF10 could be a novel therapy for ALI.

 

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