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C/EBPα Epigenetically Modulates TFF1 Expression via mC-6 Methylation in the Jejunum Inflammation Induced by a Porcine Coronavirus

Porcine epidemic diarrhea virus (PEDV) is an emerging coronavirus which causes acute diarrhea and destroys gastrointestinal barrier function in neonatal pigs. Trefoil factor 1 (TFF1) is a protective peptide for maintaining the integrity of gastrointestinal mucosa and reducing intestinal inflammation...

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Autores principales: Qu, Huan, Zong, Qiufang, Wang, Haifei, Wu, Shenglong, Cai, Demin, Bao, Wenbin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174463/
https://www.ncbi.nlm.nih.gov/pubmed/35693767
http://dx.doi.org/10.3389/fimmu.2022.881289
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author Qu, Huan
Zong, Qiufang
Wang, Haifei
Wu, Shenglong
Cai, Demin
Bao, Wenbin
author_facet Qu, Huan
Zong, Qiufang
Wang, Haifei
Wu, Shenglong
Cai, Demin
Bao, Wenbin
author_sort Qu, Huan
collection PubMed
description Porcine epidemic diarrhea virus (PEDV) is an emerging coronavirus which causes acute diarrhea and destroys gastrointestinal barrier function in neonatal pigs. Trefoil factor 1 (TFF1) is a protective peptide for maintaining the integrity of gastrointestinal mucosa and reducing intestinal inflammation. However, its role in protecting intestinal epithelium against PEDV infection is still unclear. In this study, we discovered that TFF1 expression was activated in the jejunum of pigs with PEDV infection and TFF1 is required for the growth of porcine intestinal epithelial cells. For instance, inhibited cell proliferation and cell arrest were observed when TFF1 is genetically knocked-out using CRISPR-Cas9. Additionally, TFF1 depletion increased viral copy number and PEDV titer, along with the elevated genes involved in antiviral and inflammatory cytokines. The decreased TFF1 mRNA expression is in line with hypermethylation on the gene promoter. Notably, the strong interactions of protein-DNA complexes containing CCAAT motif significantly increased C/EBPα accessibility, whereas hypermethylation of mC-6 loci decreased C/EBPα binding occupancies in TFF1 promoter. Overall, our findings show that PEDV triggers the C/EBPα-mediated epigenetic regulation of TFF1 in intestine epithelium and facilitates host resistance to PEDV and other Coronavirus infections.
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spelling pubmed-91744632022-06-09 C/EBPα Epigenetically Modulates TFF1 Expression via mC-6 Methylation in the Jejunum Inflammation Induced by a Porcine Coronavirus Qu, Huan Zong, Qiufang Wang, Haifei Wu, Shenglong Cai, Demin Bao, Wenbin Front Immunol Immunology Porcine epidemic diarrhea virus (PEDV) is an emerging coronavirus which causes acute diarrhea and destroys gastrointestinal barrier function in neonatal pigs. Trefoil factor 1 (TFF1) is a protective peptide for maintaining the integrity of gastrointestinal mucosa and reducing intestinal inflammation. However, its role in protecting intestinal epithelium against PEDV infection is still unclear. In this study, we discovered that TFF1 expression was activated in the jejunum of pigs with PEDV infection and TFF1 is required for the growth of porcine intestinal epithelial cells. For instance, inhibited cell proliferation and cell arrest were observed when TFF1 is genetically knocked-out using CRISPR-Cas9. Additionally, TFF1 depletion increased viral copy number and PEDV titer, along with the elevated genes involved in antiviral and inflammatory cytokines. The decreased TFF1 mRNA expression is in line with hypermethylation on the gene promoter. Notably, the strong interactions of protein-DNA complexes containing CCAAT motif significantly increased C/EBPα accessibility, whereas hypermethylation of mC-6 loci decreased C/EBPα binding occupancies in TFF1 promoter. Overall, our findings show that PEDV triggers the C/EBPα-mediated epigenetic regulation of TFF1 in intestine epithelium and facilitates host resistance to PEDV and other Coronavirus infections. Frontiers Media S.A. 2022-05-25 /pmc/articles/PMC9174463/ /pubmed/35693767 http://dx.doi.org/10.3389/fimmu.2022.881289 Text en Copyright © 2022 Qu, Zong, Wang, Wu, Cai and Bao 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 Immunology
Qu, Huan
Zong, Qiufang
Wang, Haifei
Wu, Shenglong
Cai, Demin
Bao, Wenbin
C/EBPα Epigenetically Modulates TFF1 Expression via mC-6 Methylation in the Jejunum Inflammation Induced by a Porcine Coronavirus
title C/EBPα Epigenetically Modulates TFF1 Expression via mC-6 Methylation in the Jejunum Inflammation Induced by a Porcine Coronavirus
title_full C/EBPα Epigenetically Modulates TFF1 Expression via mC-6 Methylation in the Jejunum Inflammation Induced by a Porcine Coronavirus
title_fullStr C/EBPα Epigenetically Modulates TFF1 Expression via mC-6 Methylation in the Jejunum Inflammation Induced by a Porcine Coronavirus
title_full_unstemmed C/EBPα Epigenetically Modulates TFF1 Expression via mC-6 Methylation in the Jejunum Inflammation Induced by a Porcine Coronavirus
title_short C/EBPα Epigenetically Modulates TFF1 Expression via mC-6 Methylation in the Jejunum Inflammation Induced by a Porcine Coronavirus
title_sort c/ebpα epigenetically modulates tff1 expression via mc-6 methylation in the jejunum inflammation induced by a porcine coronavirus
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174463/
https://www.ncbi.nlm.nih.gov/pubmed/35693767
http://dx.doi.org/10.3389/fimmu.2022.881289
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