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Acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks
Hepatic ischemia-reperfusion injury (HIRI), a common two-phase intersocietal reaction in liver surgery, typically leading to sustained liver dysfunction. During this process, liver sinusoidal endothelial cells (LSECs) are vulnerable to damage and exert senescence-associated secretory phenotype (SASP...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539705/ https://www.ncbi.nlm.nih.gov/pubmed/37781526 http://dx.doi.org/10.7150/ijbs.87332 |
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author | Jia, Kexin Zhang, Yinhao Luo, Ranyi Liu, Runping Li, Yajing Wu, Jianzhi Xie, Kaihong Liu, Jia Li, Shuo Zhou, Fei Li, Xiaojiaoyang |
author_facet | Jia, Kexin Zhang, Yinhao Luo, Ranyi Liu, Runping Li, Yajing Wu, Jianzhi Xie, Kaihong Liu, Jia Li, Shuo Zhou, Fei Li, Xiaojiaoyang |
author_sort | Jia, Kexin |
collection | PubMed |
description | Hepatic ischemia-reperfusion injury (HIRI), a common two-phase intersocietal reaction in liver surgery, typically leading to sustained liver dysfunction. During this process, liver sinusoidal endothelial cells (LSECs) are vulnerable to damage and exert senescence-associated secretory phenotype (SASP). However, how these SASP-LSECs secreted damage-associated molecular patterns (DAMPs) to impact the whole HIRI microenvironment and whether it can be reversed by therapeutics remains unknown. Here, we found that either HIRI surgery or hypoxia and reoxygenation (HR) stimulation forced LSECs into SASP and expressed HMGB1-dominated DAMPs, which were dramatically improved by acteoside (ACT). Additionally, hypoxic hepatocytes released excessive HMGB1 to LSECs and synergistically aggravated their SASP state. Mechanistically, HMGB1 bound with TLR3/TLR4 on LSECs, promoted the nuclear translocation of IRF1 and subsequent transcription of cxcl1 and Hmgb1, leading to the chemotaxis of neutrophils and accelerating immune damage in a vicious circle. Notably, ACT or HMGB1 siRNA effectively disrupted HMGB1-TLR3/4 interaction, leading to IRF1 inhibition and repairing LSEC functions, which was largely reversed by HMGB1 stimulation and IRF1-overexpressed liposomes with LSECs-targeted hyaluronic acid-derivative conjugated in mice. Collectively, ACT reversed the senescent fate of LSECs and restored sinusoidal networks by targeting HMGB1-TLR3/4-IRF1 signaling, thus providing protection against HIRI and offering the potential for new therapeutics development. |
format | Online Article Text |
id | pubmed-10539705 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-105397052023-09-30 Acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks Jia, Kexin Zhang, Yinhao Luo, Ranyi Liu, Runping Li, Yajing Wu, Jianzhi Xie, Kaihong Liu, Jia Li, Shuo Zhou, Fei Li, Xiaojiaoyang Int J Biol Sci Research Paper Hepatic ischemia-reperfusion injury (HIRI), a common two-phase intersocietal reaction in liver surgery, typically leading to sustained liver dysfunction. During this process, liver sinusoidal endothelial cells (LSECs) are vulnerable to damage and exert senescence-associated secretory phenotype (SASP). However, how these SASP-LSECs secreted damage-associated molecular patterns (DAMPs) to impact the whole HIRI microenvironment and whether it can be reversed by therapeutics remains unknown. Here, we found that either HIRI surgery or hypoxia and reoxygenation (HR) stimulation forced LSECs into SASP and expressed HMGB1-dominated DAMPs, which were dramatically improved by acteoside (ACT). Additionally, hypoxic hepatocytes released excessive HMGB1 to LSECs and synergistically aggravated their SASP state. Mechanistically, HMGB1 bound with TLR3/TLR4 on LSECs, promoted the nuclear translocation of IRF1 and subsequent transcription of cxcl1 and Hmgb1, leading to the chemotaxis of neutrophils and accelerating immune damage in a vicious circle. Notably, ACT or HMGB1 siRNA effectively disrupted HMGB1-TLR3/4 interaction, leading to IRF1 inhibition and repairing LSEC functions, which was largely reversed by HMGB1 stimulation and IRF1-overexpressed liposomes with LSECs-targeted hyaluronic acid-derivative conjugated in mice. Collectively, ACT reversed the senescent fate of LSECs and restored sinusoidal networks by targeting HMGB1-TLR3/4-IRF1 signaling, thus providing protection against HIRI and offering the potential for new therapeutics development. Ivyspring International Publisher 2023-09-18 /pmc/articles/PMC10539705/ /pubmed/37781526 http://dx.doi.org/10.7150/ijbs.87332 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Jia, Kexin Zhang, Yinhao Luo, Ranyi Liu, Runping Li, Yajing Wu, Jianzhi Xie, Kaihong Liu, Jia Li, Shuo Zhou, Fei Li, Xiaojiaoyang Acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks |
title | Acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks |
title_full | Acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks |
title_fullStr | Acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks |
title_full_unstemmed | Acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks |
title_short | Acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks |
title_sort | acteoside ameliorates hepatic ischemia-reperfusion injury via reversing the senescent fate of liver sinusoidal endothelial cells and restoring compromised sinusoidal networks |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539705/ https://www.ncbi.nlm.nih.gov/pubmed/37781526 http://dx.doi.org/10.7150/ijbs.87332 |
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