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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
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