Cargando…
Hypoxia inducible factor 1α promotes interleukin-1 receptor antagonist expression during hepatic ischemia-reperfusion injury
BACKGROUND: Ischemia-reperfusion injury (IRI) is a major risk associated with liver surgery and transplantation, and its pathological mechanism is complex. Interleukin-1 receptor antagonist (IL-1ra) can protect the liver from IRI. However, the regulatory mechanism of IL-1ra expression is still uncle...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9594012/ https://www.ncbi.nlm.nih.gov/pubmed/36304082 http://dx.doi.org/10.3748/wjg.v28.i38.5573 |
_version_ | 1784815306698391552 |
---|---|
author | Wang, Zhao-Yang Liu, Yu Li, Shi-Peng Li, Jian-Jun Zhang, Zhen Xiao, Xue-Chun Ou, Yang Wang, Hang Cai, Jin-Zhen Yang, Shuang |
author_facet | Wang, Zhao-Yang Liu, Yu Li, Shi-Peng Li, Jian-Jun Zhang, Zhen Xiao, Xue-Chun Ou, Yang Wang, Hang Cai, Jin-Zhen Yang, Shuang |
author_sort | Wang, Zhao-Yang |
collection | PubMed |
description | BACKGROUND: Ischemia-reperfusion injury (IRI) is a major risk associated with liver surgery and transplantation, and its pathological mechanism is complex. Interleukin-1 receptor antagonist (IL-1ra) can protect the liver from IRI. However, the regulatory mechanism of IL-1ra expression is still unclear. AIM: To identify the mechanism that could protect the liver in the early stage of IRI. METHODS: To screen the key genes in hepatic IRI, we performed RNA sequencing and gene enrichment analysis on liver tissue from mice with hepatic IRI. Subsequently, we verified the expression and effect of IL-1ra in hepatic IRI. We also used promoter mutagenesis and chromatin immunoprecipitation assay to search for the transcriptional regulatory sites of hypoxia-inducible factor (HIF)-1α. Finally, to explore the protective mechanism of ischemic preconditioning (IP), we examined the expression of HIF-1α and IL-1ra after IP. RESULTS: We identified IL-1ra as a key regulator in hepatic IRI. The expression of IL-1ra was significantly upregulated after hepatic IRI both in vivo and in vitro. Furthermore, we found that HIF-1α regulated Il-1ra transcription in response to hypoxia. Increased HIF-1α accumulation promoted IL-1ra expression, whereas inhibition of HIF-1α exhibited the opposite effect. We also confirmed a predominant role for hypoxia response element in the regulation of Il1ra transcription by HIF-1α activation. Of note, we demonstrated that IP protects against hepatic IRI by inducing IL-1ra expression, which is mediated through HIF-1α. CONCLUSION: We demonstrated that ischemia or hypoxia leads to increased expression of IL-1ra through HIF-1α. Importantly, IP protects the liver from IRI via the HIF-1α–IL-1ra pathway. |
format | Online Article Text |
id | pubmed-9594012 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-95940122022-10-26 Hypoxia inducible factor 1α promotes interleukin-1 receptor antagonist expression during hepatic ischemia-reperfusion injury Wang, Zhao-Yang Liu, Yu Li, Shi-Peng Li, Jian-Jun Zhang, Zhen Xiao, Xue-Chun Ou, Yang Wang, Hang Cai, Jin-Zhen Yang, Shuang World J Gastroenterol Basic Study BACKGROUND: Ischemia-reperfusion injury (IRI) is a major risk associated with liver surgery and transplantation, and its pathological mechanism is complex. Interleukin-1 receptor antagonist (IL-1ra) can protect the liver from IRI. However, the regulatory mechanism of IL-1ra expression is still unclear. AIM: To identify the mechanism that could protect the liver in the early stage of IRI. METHODS: To screen the key genes in hepatic IRI, we performed RNA sequencing and gene enrichment analysis on liver tissue from mice with hepatic IRI. Subsequently, we verified the expression and effect of IL-1ra in hepatic IRI. We also used promoter mutagenesis and chromatin immunoprecipitation assay to search for the transcriptional regulatory sites of hypoxia-inducible factor (HIF)-1α. Finally, to explore the protective mechanism of ischemic preconditioning (IP), we examined the expression of HIF-1α and IL-1ra after IP. RESULTS: We identified IL-1ra as a key regulator in hepatic IRI. The expression of IL-1ra was significantly upregulated after hepatic IRI both in vivo and in vitro. Furthermore, we found that HIF-1α regulated Il-1ra transcription in response to hypoxia. Increased HIF-1α accumulation promoted IL-1ra expression, whereas inhibition of HIF-1α exhibited the opposite effect. We also confirmed a predominant role for hypoxia response element in the regulation of Il1ra transcription by HIF-1α activation. Of note, we demonstrated that IP protects against hepatic IRI by inducing IL-1ra expression, which is mediated through HIF-1α. CONCLUSION: We demonstrated that ischemia or hypoxia leads to increased expression of IL-1ra through HIF-1α. Importantly, IP protects the liver from IRI via the HIF-1α–IL-1ra pathway. Baishideng Publishing Group Inc 2022-10-14 2022-10-14 /pmc/articles/PMC9594012/ /pubmed/36304082 http://dx.doi.org/10.3748/wjg.v28.i38.5573 Text en ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/ |
spellingShingle | Basic Study Wang, Zhao-Yang Liu, Yu Li, Shi-Peng Li, Jian-Jun Zhang, Zhen Xiao, Xue-Chun Ou, Yang Wang, Hang Cai, Jin-Zhen Yang, Shuang Hypoxia inducible factor 1α promotes interleukin-1 receptor antagonist expression during hepatic ischemia-reperfusion injury |
title | Hypoxia inducible factor 1α promotes interleukin-1 receptor antagonist expression during hepatic ischemia-reperfusion injury |
title_full | Hypoxia inducible factor 1α promotes interleukin-1 receptor antagonist expression during hepatic ischemia-reperfusion injury |
title_fullStr | Hypoxia inducible factor 1α promotes interleukin-1 receptor antagonist expression during hepatic ischemia-reperfusion injury |
title_full_unstemmed | Hypoxia inducible factor 1α promotes interleukin-1 receptor antagonist expression during hepatic ischemia-reperfusion injury |
title_short | Hypoxia inducible factor 1α promotes interleukin-1 receptor antagonist expression during hepatic ischemia-reperfusion injury |
title_sort | hypoxia inducible factor 1α promotes interleukin-1 receptor antagonist expression during hepatic ischemia-reperfusion injury |
topic | Basic Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9594012/ https://www.ncbi.nlm.nih.gov/pubmed/36304082 http://dx.doi.org/10.3748/wjg.v28.i38.5573 |
work_keys_str_mv | AT wangzhaoyang hypoxiainduciblefactor1apromotesinterleukin1receptorantagonistexpressionduringhepaticischemiareperfusioninjury AT liuyu hypoxiainduciblefactor1apromotesinterleukin1receptorantagonistexpressionduringhepaticischemiareperfusioninjury AT lishipeng hypoxiainduciblefactor1apromotesinterleukin1receptorantagonistexpressionduringhepaticischemiareperfusioninjury AT lijianjun hypoxiainduciblefactor1apromotesinterleukin1receptorantagonistexpressionduringhepaticischemiareperfusioninjury AT zhangzhen hypoxiainduciblefactor1apromotesinterleukin1receptorantagonistexpressionduringhepaticischemiareperfusioninjury AT xiaoxuechun hypoxiainduciblefactor1apromotesinterleukin1receptorantagonistexpressionduringhepaticischemiareperfusioninjury AT ouyang hypoxiainduciblefactor1apromotesinterleukin1receptorantagonistexpressionduringhepaticischemiareperfusioninjury AT wanghang hypoxiainduciblefactor1apromotesinterleukin1receptorantagonistexpressionduringhepaticischemiareperfusioninjury AT caijinzhen hypoxiainduciblefactor1apromotesinterleukin1receptorantagonistexpressionduringhepaticischemiareperfusioninjury AT yangshuang hypoxiainduciblefactor1apromotesinterleukin1receptorantagonistexpressionduringhepaticischemiareperfusioninjury |