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Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research

Acute lung injury (ALI) is a potentially life-threatening, devastating disease with an extremely high rate of mortality. The underlying mechanism of ALI is currently unclear. In this study, we aimed to confirm the hub genes associated with ALI and explore their functions and molecular mechanisms usi...

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Autores principales: Qu, Lihua, Li, Yi, Chen, Chao, Yin, Tong, Fang, Qian, Zhao, Yijin, Lv, Wenting, Liu, Ziqi, Chen, Yangye, Shen, Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357074/
https://www.ncbi.nlm.nih.gov/pubmed/35933468
http://dx.doi.org/10.1038/s41419-022-05134-8
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author Qu, Lihua
Li, Yi
Chen, Chao
Yin, Tong
Fang, Qian
Zhao, Yijin
Lv, Wenting
Liu, Ziqi
Chen, Yangye
Shen, Li
author_facet Qu, Lihua
Li, Yi
Chen, Chao
Yin, Tong
Fang, Qian
Zhao, Yijin
Lv, Wenting
Liu, Ziqi
Chen, Yangye
Shen, Li
author_sort Qu, Lihua
collection PubMed
description Acute lung injury (ALI) is a potentially life-threatening, devastating disease with an extremely high rate of mortality. The underlying mechanism of ALI is currently unclear. In this study, we aimed to confirm the hub genes associated with ALI and explore their functions and molecular mechanisms using bioinformatics methods. Five microarray datasets available in GEO were used to perform Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs) and the key genes were identified via the protein-protein interaction (PPI) network. Lipopolysaccharide intraperitoneal injection was administered to establish an ALI model. Overall, 40 robust DEGs, which are mainly involved in the inflammatory response, protein catabolic process, and NF-κB signaling pathway were identified. Among these DEGs, we identified two genes associated with ALI, of which the CAV-1/NF-κB axis was significantly upregulated in ALI, and was identified as one of the most effective targets for ALI prevention. Subsequently, the expression of CAV-1 was knocked down using AAV-shCAV-1 or CAV-1-siRNA to study its effect on the pathogenesis of ALI in vivo and in vitro. The results of this study indicated that CAV-1/NF-κB axis levels were elevated in vivo and in vitro, accompanied by an increase in lung inflammation and autophagy. The knockdown of CAV-1 may improve ALI. Mechanistically, inflammation was reduced mainly by decreasing the expression levels of CD3 and F4/80, and activating autophagy by inhibiting AKT/mTOR and promoting the AMPK signaling pathway. Taken together, this study provides crucial evidence that CAV-1 knockdown inhibits the occurrence of ALI, suggesting that the CAV-1/NF-κB axis may be a promising therapeutic target for ALI treatment.
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spelling pubmed-93570742022-08-08 Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research Qu, Lihua Li, Yi Chen, Chao Yin, Tong Fang, Qian Zhao, Yijin Lv, Wenting Liu, Ziqi Chen, Yangye Shen, Li Cell Death Dis Article Acute lung injury (ALI) is a potentially life-threatening, devastating disease with an extremely high rate of mortality. The underlying mechanism of ALI is currently unclear. In this study, we aimed to confirm the hub genes associated with ALI and explore their functions and molecular mechanisms using bioinformatics methods. Five microarray datasets available in GEO were used to perform Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs) and the key genes were identified via the protein-protein interaction (PPI) network. Lipopolysaccharide intraperitoneal injection was administered to establish an ALI model. Overall, 40 robust DEGs, which are mainly involved in the inflammatory response, protein catabolic process, and NF-κB signaling pathway were identified. Among these DEGs, we identified two genes associated with ALI, of which the CAV-1/NF-κB axis was significantly upregulated in ALI, and was identified as one of the most effective targets for ALI prevention. Subsequently, the expression of CAV-1 was knocked down using AAV-shCAV-1 or CAV-1-siRNA to study its effect on the pathogenesis of ALI in vivo and in vitro. The results of this study indicated that CAV-1/NF-κB axis levels were elevated in vivo and in vitro, accompanied by an increase in lung inflammation and autophagy. The knockdown of CAV-1 may improve ALI. Mechanistically, inflammation was reduced mainly by decreasing the expression levels of CD3 and F4/80, and activating autophagy by inhibiting AKT/mTOR and promoting the AMPK signaling pathway. Taken together, this study provides crucial evidence that CAV-1 knockdown inhibits the occurrence of ALI, suggesting that the CAV-1/NF-κB axis may be a promising therapeutic target for ALI treatment. Nature Publishing Group UK 2022-08-06 /pmc/articles/PMC9357074/ /pubmed/35933468 http://dx.doi.org/10.1038/s41419-022-05134-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Qu, Lihua
Li, Yi
Chen, Chao
Yin, Tong
Fang, Qian
Zhao, Yijin
Lv, Wenting
Liu, Ziqi
Chen, Yangye
Shen, Li
Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research
title Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research
title_full Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research
title_fullStr Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research
title_full_unstemmed Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research
title_short Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research
title_sort caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357074/
https://www.ncbi.nlm.nih.gov/pubmed/35933468
http://dx.doi.org/10.1038/s41419-022-05134-8
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