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Inflammation
Published in: Inflammation 1/2024

Open Access 21-10-2023 | Acute Respiratory Distress-Syndrome | RESEARCH

Fibroblast Growth Factor 21 Relieves Lipopolysaccharide-Induced Acute Lung Injury by Suppressing JAK2/STAT3 Signaling Pathway

Authors: Mengsi Cai, Huihui Ye, Xiayan Zhu, Xiuchun Li, Luqiong Cai, Jiajia Jin, Qiwen Chen, Yuzhe Shi, Lehe Yang, Liangxing Wang, Xiaoying Huang

Published in: Inflammation | Issue 1/2024

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Abstract

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life‐threatening disease without an effective drug at present. Fibroblast growth factor 21 (FGF21) was reported to be protective against inflammation in metabolic disease in recent studies. However, the role of FGF21 in ALI has been rarely investigated. In this study, it was found that the expression of FGF21 was markedly increased in lung tissue under lipopolysaccharide (LPS) stimulation in vivo, whereas it was decreased in lung epithelial cells under LPS stimulation in vitro. Therefore, our research aimed to elucidate the potential role of FGF21 in LPS-induced ALI and to detect possible underlying mechanisms. The results revealed that the deficiency of FGF21 aggravated pathological damage, inflammatory infiltration, and pulmonary function in LPS-induced ALI, while exogenous administration of FGF21 improved these manifestations. Moreover, through RNA sequencing and enrichment analysis, it was unveiled that FGF21 might play a protective role in LPS-induced ALI via JAK2/STAT3 signaling pathway. The therapeutic effect of FGF21 was weakened after additional usage of JAK2 activator in vivo. Further investigation revealed that FGF21 significantly inhibited STAT3 phosphorylation and impaired the nuclear translocation of STAT3 in vitro. In addition, the aggravation of inflammation caused by silencing FGF21 can be alleviated by JAK2 inhibitor in vitro. Collectively, these findings unveil a potent protective effect of FGF21 against LPS-induced ALI by inhibiting the JAK2/STAT3 pathway, implying that FGF21 might be a novel and effective therapy for ALI.
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Metadata
Title
Fibroblast Growth Factor 21 Relieves Lipopolysaccharide-Induced Acute Lung Injury by Suppressing JAK2/STAT3 Signaling Pathway
Authors
Mengsi Cai
Huihui Ye
Xiayan Zhu
Xiuchun Li
Luqiong Cai
Jiajia Jin
Qiwen Chen
Yuzhe Shi
Lehe Yang
Liangxing Wang
Xiaoying Huang
Publication date
21-10-2023
Publisher
Springer US
Published in
Inflammation / Issue 1/2024
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-023-01905-3

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