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LncRNA Gm26917 regulates inflammatory response in macrophages by enhancing Annexin A1 ubiquitination in LPS-induced acute liver injury

Long noncoding RNAs (lncRNAs) are defined as transcripts of more than 200 nucleotides that have little or no coding potential. LncRNAs function as key regulators in diverse physiological and pathological processes. However, the roles of lncRNAs in lipopolysaccharide (LPS)-induced acute liver injury...

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Autores principales: Zhao, Qing, Sheng, Meng-Fei, Wang, Yao-Yun, Wang, Xing-Yu, Liu, Wei-Yi, Zhang, Yuan-Yuan, Ke, Tiao-Ying, Chen, Shu, Pang, Gao-Zong, Yong, Liang, Ding, Zhan, Shen, Yu-Jun, Shen, Yu-Xian, Shao, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9663662/
https://www.ncbi.nlm.nih.gov/pubmed/36386180
http://dx.doi.org/10.3389/fphar.2022.975250
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author Zhao, Qing
Sheng, Meng-Fei
Wang, Yao-Yun
Wang, Xing-Yu
Liu, Wei-Yi
Zhang, Yuan-Yuan
Ke, Tiao-Ying
Chen, Shu
Pang, Gao-Zong
Yong, Liang
Ding, Zhan
Shen, Yu-Jun
Shen, Yu-Xian
Shao, Wei
author_facet Zhao, Qing
Sheng, Meng-Fei
Wang, Yao-Yun
Wang, Xing-Yu
Liu, Wei-Yi
Zhang, Yuan-Yuan
Ke, Tiao-Ying
Chen, Shu
Pang, Gao-Zong
Yong, Liang
Ding, Zhan
Shen, Yu-Jun
Shen, Yu-Xian
Shao, Wei
author_sort Zhao, Qing
collection PubMed
description Long noncoding RNAs (lncRNAs) are defined as transcripts of more than 200 nucleotides that have little or no coding potential. LncRNAs function as key regulators in diverse physiological and pathological processes. However, the roles of lncRNAs in lipopolysaccharide (LPS)-induced acute liver injury (ALI) are still elusive. In this study, we report the roles of lncRNA Gm26917 induced by LPS in modulating liver inflammation. As key components of the innate immune system, macrophages play critical roles in the initiation, progression and resolution of ALI. Our studies demonstrated that Gm26917 localized in the cytoplasm of hepatic macrophages and globally regulated the expression of inflammatory genes and the differentiation of macrophages. In vivo study showed that lentivirus-mediated gene silencing of Gm26917 attenuated liver inflammation and protected mice from LPS-induced ALI. Furthermore, mechanistic study showed that the 3′-truncation of Gm26917 interacted with the N-terminus of Annexin A1, a negative regulator of the NF-κB signaling pathway. We also found that Gm26917 knockdown suppressed NF-κB activity by decreasing the ubiquitination of Annexin A1 and its interaction with NEMO. In addition, expression of Gm26917 in inflammatory macrophages was regulated by the transcription factor forkhead box M1 (FOXM1). LPS treatment dramatically increased the binding of FOXM1 to the promoter region of Gm26917 in macrophages. In summary, our findings suggest that lncRNA Gm26917 silencing protects against LPS-induced liver injury by regulating the TLR4/NF-κB signaling pathway in macrophages.
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spelling pubmed-96636622022-11-15 LncRNA Gm26917 regulates inflammatory response in macrophages by enhancing Annexin A1 ubiquitination in LPS-induced acute liver injury Zhao, Qing Sheng, Meng-Fei Wang, Yao-Yun Wang, Xing-Yu Liu, Wei-Yi Zhang, Yuan-Yuan Ke, Tiao-Ying Chen, Shu Pang, Gao-Zong Yong, Liang Ding, Zhan Shen, Yu-Jun Shen, Yu-Xian Shao, Wei Front Pharmacol Pharmacology Long noncoding RNAs (lncRNAs) are defined as transcripts of more than 200 nucleotides that have little or no coding potential. LncRNAs function as key regulators in diverse physiological and pathological processes. However, the roles of lncRNAs in lipopolysaccharide (LPS)-induced acute liver injury (ALI) are still elusive. In this study, we report the roles of lncRNA Gm26917 induced by LPS in modulating liver inflammation. As key components of the innate immune system, macrophages play critical roles in the initiation, progression and resolution of ALI. Our studies demonstrated that Gm26917 localized in the cytoplasm of hepatic macrophages and globally regulated the expression of inflammatory genes and the differentiation of macrophages. In vivo study showed that lentivirus-mediated gene silencing of Gm26917 attenuated liver inflammation and protected mice from LPS-induced ALI. Furthermore, mechanistic study showed that the 3′-truncation of Gm26917 interacted with the N-terminus of Annexin A1, a negative regulator of the NF-κB signaling pathway. We also found that Gm26917 knockdown suppressed NF-κB activity by decreasing the ubiquitination of Annexin A1 and its interaction with NEMO. In addition, expression of Gm26917 in inflammatory macrophages was regulated by the transcription factor forkhead box M1 (FOXM1). LPS treatment dramatically increased the binding of FOXM1 to the promoter region of Gm26917 in macrophages. In summary, our findings suggest that lncRNA Gm26917 silencing protects against LPS-induced liver injury by regulating the TLR4/NF-κB signaling pathway in macrophages. Frontiers Media S.A. 2022-11-01 /pmc/articles/PMC9663662/ /pubmed/36386180 http://dx.doi.org/10.3389/fphar.2022.975250 Text en Copyright © 2022 Zhao, Sheng, Wang, Wang, Liu, Zhang, Ke, Chen, Pang, Yong, Ding, Shen, Shen and Shao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhao, Qing
Sheng, Meng-Fei
Wang, Yao-Yun
Wang, Xing-Yu
Liu, Wei-Yi
Zhang, Yuan-Yuan
Ke, Tiao-Ying
Chen, Shu
Pang, Gao-Zong
Yong, Liang
Ding, Zhan
Shen, Yu-Jun
Shen, Yu-Xian
Shao, Wei
LncRNA Gm26917 regulates inflammatory response in macrophages by enhancing Annexin A1 ubiquitination in LPS-induced acute liver injury
title LncRNA Gm26917 regulates inflammatory response in macrophages by enhancing Annexin A1 ubiquitination in LPS-induced acute liver injury
title_full LncRNA Gm26917 regulates inflammatory response in macrophages by enhancing Annexin A1 ubiquitination in LPS-induced acute liver injury
title_fullStr LncRNA Gm26917 regulates inflammatory response in macrophages by enhancing Annexin A1 ubiquitination in LPS-induced acute liver injury
title_full_unstemmed LncRNA Gm26917 regulates inflammatory response in macrophages by enhancing Annexin A1 ubiquitination in LPS-induced acute liver injury
title_short LncRNA Gm26917 regulates inflammatory response in macrophages by enhancing Annexin A1 ubiquitination in LPS-induced acute liver injury
title_sort lncrna gm26917 regulates inflammatory response in macrophages by enhancing annexin a1 ubiquitination in lps-induced acute liver injury
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9663662/
https://www.ncbi.nlm.nih.gov/pubmed/36386180
http://dx.doi.org/10.3389/fphar.2022.975250
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