Lithocholic acid attenuates DON-induced inflammatory responses via epigenetic regulation of DUSP5 and TRAF5 in porcine intestinal epithelial cells
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 stud...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Veterinary Science |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fvets.2025.1493496/full |
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| author | Shiqi Wang Xiaoxu Peng Qi Zhu Sichen Lu Ping Hu In Ho Kim Hao-Yu Liu Hao-Yu Liu Wael Ennab Madesh Muniyappan Demin Cai Demin Cai |
| author_facet | Shiqi Wang Xiaoxu Peng Qi Zhu Sichen Lu Ping Hu In Ho Kim Hao-Yu Liu Hao-Yu Liu Wael Ennab Madesh Muniyappan Demin Cai Demin Cai |
| author_sort | Shiqi Wang |
| collection | DOAJ |
| description | 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, 250 ng/mL DON, 20 μmol/L LCA, 250 ng/mL DON+ 20 μmol/L LCA for 24 h 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. |
| format | Article |
| id | doaj-art-67e22fa29f76497aab9dbec0ce4178a2 |
| institution | DOAJ |
| issn | 2297-1769 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Veterinary Science |
| spelling | doaj-art-67e22fa29f76497aab9dbec0ce4178a22025-08-20T02:45:56ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692025-02-011210.3389/fvets.2025.14934961493496Lithocholic acid attenuates DON-induced inflammatory responses via epigenetic regulation of DUSP5 and TRAF5 in porcine intestinal epithelial cellsShiqi Wang0Xiaoxu Peng1Qi Zhu2Sichen Lu3Ping Hu4In Ho Kim5Hao-Yu Liu6Hao-Yu Liu7Wael Ennab8Madesh Muniyappan9Demin Cai10Demin Cai11College of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaCollege of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaCollege of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaCollege of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaCollege of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaDepartment of Animal Resource and Science, Dankook University, Cheonan, Choongnam, Republic of KoreaCollege of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaJiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaCollege of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaCollege of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaCollege of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaJiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou, ChinaDeoxynivalenol (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, 250 ng/mL DON, 20 μmol/L LCA, 250 ng/mL DON+ 20 μmol/L LCA for 24 h 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.https://www.frontiersin.org/articles/10.3389/fvets.2025.1493496/fullepigeneticshistone modificationporcinedeoxynivalenollithocholic acid |
| spellingShingle | Shiqi Wang Xiaoxu Peng Qi Zhu Sichen Lu Ping Hu In Ho Kim Hao-Yu Liu Hao-Yu Liu Wael Ennab Madesh Muniyappan Demin Cai Demin Cai Lithocholic acid attenuates DON-induced inflammatory responses via epigenetic regulation of DUSP5 and TRAF5 in porcine intestinal epithelial cells Frontiers in Veterinary Science epigenetics histone modification porcine deoxynivalenol lithocholic acid |
| title | Lithocholic acid attenuates DON-induced inflammatory responses via epigenetic regulation of DUSP5 and TRAF5 in porcine intestinal epithelial cells |
| title_full | Lithocholic acid attenuates DON-induced inflammatory responses via epigenetic regulation of DUSP5 and TRAF5 in porcine intestinal epithelial cells |
| title_fullStr | Lithocholic acid attenuates DON-induced inflammatory responses via epigenetic regulation of DUSP5 and TRAF5 in porcine intestinal epithelial cells |
| title_full_unstemmed | Lithocholic acid attenuates DON-induced inflammatory responses via epigenetic regulation of DUSP5 and TRAF5 in porcine intestinal epithelial cells |
| title_short | Lithocholic acid attenuates DON-induced inflammatory responses via epigenetic regulation of DUSP5 and TRAF5 in porcine intestinal epithelial cells |
| title_sort | lithocholic acid attenuates don induced inflammatory responses via epigenetic regulation of dusp5 and traf5 in porcine intestinal epithelial cells |
| topic | epigenetics histone modification porcine deoxynivalenol lithocholic acid |
| url | https://www.frontiersin.org/articles/10.3389/fvets.2025.1493496/full |
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