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BRIEF RESEARCH REPORT article
Front. Vet. Sci.
Sec. Livestock Genomics
Volume 12 - 2025 | doi: 10.3389/fvets.2025.1493496
This article is part of the Research Topic Epigenetics and multi-omics studies of important traits in livestock View all articles
Lithocholic Acid Attenuates DON-Induced Inflammatory Responses via Epigenetic Regulation of DUSP5 and TRAF5 in Porcine Intestinal Epithelial Cells
Provisionally accepted
Shiqi Wang 1
Xiao Xu Peng 1
Qi Zhu 1 Sichen Lu 1
Ping Hu 1
In Ho Kim 2
Haoyu Liu 1
MUNIYAPPAN MADESH 1*
Wael Ennab 1
Demin Cai 1*- 1 Yangzhou University, Yangzhou, China
- 2 Department of Animal Resources, Dankook University, Cheonan, South Chungcheong, Republic of Korea
Deoxynivalenol (DON) is the most common mycotoxin that frequently contaminates human food and animal feed, resulting in intestinal diseases and systemic immunosuppression. Lithocholic acid (LCA) exhibits various pharmacological activities. RNA-seq and ChIP-qPCR analysis were used in the current study to investigate the protective mechanism of LCA for DON-induced inflammatory Responses via Epigenetic Regulation of DUSP5 and TRAF5 in porcine ileal epithelial cell lines (IPI-2I) cells. The IPI-2I cells were treated with the vehicle group, 250ng/mL DON, 20 μmol/L LCA, 250ng/mL DON+ 20 μmol/L LCA for 24 hours could induce inflammatory Responses via Epigenetic Regulation of DUSP5 and TRAF5 in IPI-2I cells. By analyzing the transcriptional profiles of DON and LCA-treated IPI-2I, we observed significant transcriptional changes in IPI-2I cells. Further analysis of up-and down-regulated differential genes revealed the enrichment of pathways closely related to inflammation and apoptosis, such as the MAPK signaling pathway, IL17 signaling pathway, and Wnt signaling pathway. An upregulated (P <0.05) relative mRNA expression level of RAP1B, GDNF, FGF2, IL1R1, RAPGEF2, DUSP5, TGFB3, CACNA1G, TEK and RPS6KA2 were noted in IPI-2I exposed to DON. DON-exposed IPI-2I cells dramatically enhanced (P < 0.05) histone marks associated with transcriptional activation, H3K9ac, H3K18ac, H3K27ac, H3K4me1, H3K9bhb, H3K18bhb Pol-II and Ser5 Pol-II at the enhancers of DUSP5 and TRAF5. Overall, our findings provide a theoretical basis for understanding the mechanism of action of LCA in attenuating DON-induced intestinal injury and for better understanding the potential of LCA as a treatment or prevention of mycotoxin-associated intestinal diseases in swine production.
Keywords: epigenetics, histone modification, porcine, Deoxynivalenol, Lithocholic Acid
Received: 09 Sep 2024; Accepted: 10 Feb 2025.
Copyright: © 2025 Wang, Peng, Zhu, Lu, Hu, Kim, Liu, MADESH, Ennab and Cai. 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) or licensor 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.
* Correspondence:
MUNIYAPPAN MADESH, Yangzhou University, Yangzhou, China
Demin Cai, Yangzhou University, Yangzhou, China
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