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Protective role of down-regulated microRNA-31 on intestinal barrier dysfunction through inhibition of NF-κB/HIF-1α pathway by binding to HMOX1 in rats with sepsis

BACKGROUND: Intestinal barrier dysfunction is a significant clinical problem, commonly developing in a variety of acute or chronic pathological conditions. Herein, we evaluate the effect of microRNA-31 (miR-31) on intestinal barrier dysfunction through NF-κB/HIF-1α pathway by targeting HMOX1 in rats...

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Autores principales: Zhan, Cheng-Ye, Chen, Di, Luo, Jin-Long, Shi, Ying-Hua, Zhang, You-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194748/
https://www.ncbi.nlm.nih.gov/pubmed/30340459
http://dx.doi.org/10.1186/s10020-018-0053-2
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author Zhan, Cheng-Ye
Chen, Di
Luo, Jin-Long
Shi, Ying-Hua
Zhang, You-Ping
author_facet Zhan, Cheng-Ye
Chen, Di
Luo, Jin-Long
Shi, Ying-Hua
Zhang, You-Ping
author_sort Zhan, Cheng-Ye
collection PubMed
description BACKGROUND: Intestinal barrier dysfunction is a significant clinical problem, commonly developing in a variety of acute or chronic pathological conditions. Herein, we evaluate the effect of microRNA-31 (miR-31) on intestinal barrier dysfunction through NF-κB/HIF-1α pathway by targeting HMOX1 in rats with sepsis. METHODS: Male Sprague-Dawley rats were collected and divided into the sham group, and the cecum ligation and perforation group which was subdivided after CACO-2 cell transfection of different mimic, inhibitor, or siRNA. Levels of serum D-lactic acid, diamine oxidase and fluorescence isothiocyanate dextran, FITC-DX concentration, and bacterial translocation were detected. Superoxidedismutase (SOD) activity and malondialdehyde (MDA) content were evaluated using the colorimetric method and an automatic microplate reader, respectively. Additionally, the levels of tumor necrosis factor, interleukin (IL)-6, and IL-10 were tested using enzyme-linked immunosorbent assay. The expression of miR-31, HMOX1, NF-κB, HIF-1α, IκB, ZO-1 and Occludin were assessed by reverse transcription quantitative polymerase chain reaction and Western blot analysis. RESULTS: Inhibition of miR-31 decreased intestinal mucosal permeability and intestinal barrier function. The increased levels of miR-31 could cause oxidative damage and affect the expression of inflammatory factors in intestinal tissue of rats. HMOX1 was confirmed as a target gene of miR-31. MiR-31 affected intestinal mucosal permeability and intestinal barrier function, as well as oxidative damage and inflammation level by regulating HMOX1. Down-regulation of miR-31 inhibited NF-κB/HIF-1α pathway related genes by regulating HMOX1 expression. Furthermore, inhibition of miR-31 increased survival rates of rats. CONCLUSION: Overall, the current study found that inhibition of miR-31 protects against intestinal barrier dysfunction through suppression of the NF-κB/HIF-1α pathway by targeting HMOX1 in rats with sepsis.
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spelling pubmed-61947482018-10-31 Protective role of down-regulated microRNA-31 on intestinal barrier dysfunction through inhibition of NF-κB/HIF-1α pathway by binding to HMOX1 in rats with sepsis Zhan, Cheng-Ye Chen, Di Luo, Jin-Long Shi, Ying-Hua Zhang, You-Ping Mol Med Research Article BACKGROUND: Intestinal barrier dysfunction is a significant clinical problem, commonly developing in a variety of acute or chronic pathological conditions. Herein, we evaluate the effect of microRNA-31 (miR-31) on intestinal barrier dysfunction through NF-κB/HIF-1α pathway by targeting HMOX1 in rats with sepsis. METHODS: Male Sprague-Dawley rats were collected and divided into the sham group, and the cecum ligation and perforation group which was subdivided after CACO-2 cell transfection of different mimic, inhibitor, or siRNA. Levels of serum D-lactic acid, diamine oxidase and fluorescence isothiocyanate dextran, FITC-DX concentration, and bacterial translocation were detected. Superoxidedismutase (SOD) activity and malondialdehyde (MDA) content were evaluated using the colorimetric method and an automatic microplate reader, respectively. Additionally, the levels of tumor necrosis factor, interleukin (IL)-6, and IL-10 were tested using enzyme-linked immunosorbent assay. The expression of miR-31, HMOX1, NF-κB, HIF-1α, IκB, ZO-1 and Occludin were assessed by reverse transcription quantitative polymerase chain reaction and Western blot analysis. RESULTS: Inhibition of miR-31 decreased intestinal mucosal permeability and intestinal barrier function. The increased levels of miR-31 could cause oxidative damage and affect the expression of inflammatory factors in intestinal tissue of rats. HMOX1 was confirmed as a target gene of miR-31. MiR-31 affected intestinal mucosal permeability and intestinal barrier function, as well as oxidative damage and inflammation level by regulating HMOX1. Down-regulation of miR-31 inhibited NF-κB/HIF-1α pathway related genes by regulating HMOX1 expression. Furthermore, inhibition of miR-31 increased survival rates of rats. CONCLUSION: Overall, the current study found that inhibition of miR-31 protects against intestinal barrier dysfunction through suppression of the NF-κB/HIF-1α pathway by targeting HMOX1 in rats with sepsis. BioMed Central 2018-10-19 /pmc/articles/PMC6194748/ /pubmed/30340459 http://dx.doi.org/10.1186/s10020-018-0053-2 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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 Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zhan, Cheng-Ye
Chen, Di
Luo, Jin-Long
Shi, Ying-Hua
Zhang, You-Ping
Protective role of down-regulated microRNA-31 on intestinal barrier dysfunction through inhibition of NF-κB/HIF-1α pathway by binding to HMOX1 in rats with sepsis
title Protective role of down-regulated microRNA-31 on intestinal barrier dysfunction through inhibition of NF-κB/HIF-1α pathway by binding to HMOX1 in rats with sepsis
title_full Protective role of down-regulated microRNA-31 on intestinal barrier dysfunction through inhibition of NF-κB/HIF-1α pathway by binding to HMOX1 in rats with sepsis
title_fullStr Protective role of down-regulated microRNA-31 on intestinal barrier dysfunction through inhibition of NF-κB/HIF-1α pathway by binding to HMOX1 in rats with sepsis
title_full_unstemmed Protective role of down-regulated microRNA-31 on intestinal barrier dysfunction through inhibition of NF-κB/HIF-1α pathway by binding to HMOX1 in rats with sepsis
title_short Protective role of down-regulated microRNA-31 on intestinal barrier dysfunction through inhibition of NF-κB/HIF-1α pathway by binding to HMOX1 in rats with sepsis
title_sort protective role of down-regulated microrna-31 on intestinal barrier dysfunction through inhibition of nf-κb/hif-1α pathway by binding to hmox1 in rats with sepsis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194748/
https://www.ncbi.nlm.nih.gov/pubmed/30340459
http://dx.doi.org/10.1186/s10020-018-0053-2
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