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FGF1 alleviates LPS-induced acute lung injury via suppression of inflammation and oxidative stress

BACKGROUND: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are devastating clinical disorders with high mortality, and for which more effective therapies are urgently needed. FGF1, the prototype member of the FGF family, is shown to exert protective effects...

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Autores principales: Dhlamini, Qhaweni, Wang, Wei, Feng, Guifeng, Chen, Aiping, Chong, Lei, Li, Xue, Li, Quan, Wu, Jin, Zhou, Depu, Wang, Jie, Zhang, Hailin, Zhang, Jin-San
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238076/
https://www.ncbi.nlm.nih.gov/pubmed/35764933
http://dx.doi.org/10.1186/s10020-022-00502-8
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author Dhlamini, Qhaweni
Wang, Wei
Feng, Guifeng
Chen, Aiping
Chong, Lei
Li, Xue
Li, Quan
Wu, Jin
Zhou, Depu
Wang, Jie
Zhang, Hailin
Zhang, Jin-San
author_facet Dhlamini, Qhaweni
Wang, Wei
Feng, Guifeng
Chen, Aiping
Chong, Lei
Li, Xue
Li, Quan
Wu, Jin
Zhou, Depu
Wang, Jie
Zhang, Hailin
Zhang, Jin-San
author_sort Dhlamini, Qhaweni
collection PubMed
description BACKGROUND: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are devastating clinical disorders with high mortality, and for which more effective therapies are urgently needed. FGF1, the prototype member of the FGF family, is shown to exert protective effects against injurious stimuli in multiple disease models. Here we aimed to evaluate whether FGF1 pretreatment is protective against LPS-induced ALI and elucidate the potential underlying mechanisms. METHODS: For drug-treated groups, C57B/6 mice received a single i.p. injection of FGF1 (1 mg/kg) 1 h before the LPS challenge or not. To induce the ALI model, the mice were treated by intratracheal instillation of LPS (5 mg/kg). Then, histopathological changes in lung tissues were assessed by hematoxylin and eosin staining and transmission electron microscopy. ELISA and qPCR assays were used to detect pro-inflammatory cytokine levels in BALF and lung tissues, respectively. The total number of inflammatory cells (neutrophils and macrophages) in BALF were counted using the Wright-Giemsa method. The expressions of reactive oxygen species (ROS) and malondialdehyde (MDA) were measured using their respective kits. Western blot and immunostaining were used to evaluate the expressions of antioxidants (Nrf-2, HO-1, SOD2, GPX4, and Catalase), as well as the inflammatory and/or apoptosis-related factors (TLR4, NF-κB, and Cleaved- caspase 3). RESULTS: FGF1 pretreatment significantly ameliorated the LPS-induced histopathological changes, reduced lung wet/dry ratios, ROS and MDA levels, total BALF protein, inflammatory cell infiltration, proinflammatory cytokine levels, and significantly increased the expression of antioxidant proteins (Nrf-2, HO-1, Catalase, and SOD2). In addition, FGF1 pretreatment significantly reduced the expression of TLR4 and cleaved- caspase 3, inhibited NF-κB activation, and reduced LPS-induced cell apoptosis. CONCLUSIONS: Altogether, our results suggest that FGF1 pretreatment is protective against LPS-induced ALI through mediating anti-inflammatory and antioxidant effects, which may be attributed to the downregulation of TLR4 expression and inhibition of NF-κB activation, as well as promotion of antioxidant defenses. Therefore, FGF1 administration may prove beneficial in preventative strategies for ALI/ARDS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-022-00502-8.
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spelling pubmed-92380762022-06-29 FGF1 alleviates LPS-induced acute lung injury via suppression of inflammation and oxidative stress Dhlamini, Qhaweni Wang, Wei Feng, Guifeng Chen, Aiping Chong, Lei Li, Xue Li, Quan Wu, Jin Zhou, Depu Wang, Jie Zhang, Hailin Zhang, Jin-San Mol Med Research Article BACKGROUND: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are devastating clinical disorders with high mortality, and for which more effective therapies are urgently needed. FGF1, the prototype member of the FGF family, is shown to exert protective effects against injurious stimuli in multiple disease models. Here we aimed to evaluate whether FGF1 pretreatment is protective against LPS-induced ALI and elucidate the potential underlying mechanisms. METHODS: For drug-treated groups, C57B/6 mice received a single i.p. injection of FGF1 (1 mg/kg) 1 h before the LPS challenge or not. To induce the ALI model, the mice were treated by intratracheal instillation of LPS (5 mg/kg). Then, histopathological changes in lung tissues were assessed by hematoxylin and eosin staining and transmission electron microscopy. ELISA and qPCR assays were used to detect pro-inflammatory cytokine levels in BALF and lung tissues, respectively. The total number of inflammatory cells (neutrophils and macrophages) in BALF were counted using the Wright-Giemsa method. The expressions of reactive oxygen species (ROS) and malondialdehyde (MDA) were measured using their respective kits. Western blot and immunostaining were used to evaluate the expressions of antioxidants (Nrf-2, HO-1, SOD2, GPX4, and Catalase), as well as the inflammatory and/or apoptosis-related factors (TLR4, NF-κB, and Cleaved- caspase 3). RESULTS: FGF1 pretreatment significantly ameliorated the LPS-induced histopathological changes, reduced lung wet/dry ratios, ROS and MDA levels, total BALF protein, inflammatory cell infiltration, proinflammatory cytokine levels, and significantly increased the expression of antioxidant proteins (Nrf-2, HO-1, Catalase, and SOD2). In addition, FGF1 pretreatment significantly reduced the expression of TLR4 and cleaved- caspase 3, inhibited NF-κB activation, and reduced LPS-induced cell apoptosis. CONCLUSIONS: Altogether, our results suggest that FGF1 pretreatment is protective against LPS-induced ALI through mediating anti-inflammatory and antioxidant effects, which may be attributed to the downregulation of TLR4 expression and inhibition of NF-κB activation, as well as promotion of antioxidant defenses. Therefore, FGF1 administration may prove beneficial in preventative strategies for ALI/ARDS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-022-00502-8. BioMed Central 2022-06-28 /pmc/articles/PMC9238076/ /pubmed/35764933 http://dx.doi.org/10.1186/s10020-022-00502-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Dhlamini, Qhaweni
Wang, Wei
Feng, Guifeng
Chen, Aiping
Chong, Lei
Li, Xue
Li, Quan
Wu, Jin
Zhou, Depu
Wang, Jie
Zhang, Hailin
Zhang, Jin-San
FGF1 alleviates LPS-induced acute lung injury via suppression of inflammation and oxidative stress
title FGF1 alleviates LPS-induced acute lung injury via suppression of inflammation and oxidative stress
title_full FGF1 alleviates LPS-induced acute lung injury via suppression of inflammation and oxidative stress
title_fullStr FGF1 alleviates LPS-induced acute lung injury via suppression of inflammation and oxidative stress
title_full_unstemmed FGF1 alleviates LPS-induced acute lung injury via suppression of inflammation and oxidative stress
title_short FGF1 alleviates LPS-induced acute lung injury via suppression of inflammation and oxidative stress
title_sort fgf1 alleviates lps-induced acute lung injury via suppression of inflammation and oxidative stress
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238076/
https://www.ncbi.nlm.nih.gov/pubmed/35764933
http://dx.doi.org/10.1186/s10020-022-00502-8
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