Zearalenone-Induced Mechanical Damage of Intestinal Barrier via the RhoA/ROCK Signaling Pathway in IPEC-J2 Cells
Zearalenone (ZEN) is a widespread contaminant of cereals and agricultural products which causes food safety issues. Ingesting food or feed contaminated with ZEN can disrupt the intestinal epithelial barrier function. The RhoA/ROCK signaling pathway plays a key role in regulating the epithelial barri...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/20/12550 |
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| author | Biying Huang Jingjing Wang Aixin Gu Tianhu Wang Jianping Li Anshan Shan |
| author_facet | Biying Huang Jingjing Wang Aixin Gu Tianhu Wang Jianping Li Anshan Shan |
| author_sort | Biying Huang |
| collection | DOAJ |
| description | Zearalenone (ZEN) is a widespread contaminant of cereals and agricultural products which causes food safety issues. Ingesting food or feed contaminated with ZEN can disrupt the intestinal epithelial barrier function. The RhoA/ROCK signaling pathway plays a key role in regulating the epithelial barrier function, but studies on such roles have rarely focused on the intestine. The aim of this experiment was to investigate the exact mechanism of ZEN-induced intestinal barrier damage and whether the RhoA/ROCK signaling pathway is involved. The results showed that ZEN significantly induced alkaline phosphatase (AP) activity and FITC–dextran (4 kDa) passage across the epithelial barrier, which significantly reduced the transepithelial resistance (TEER). Meanwhile, ZEN could induce the significantly down-regulated mRNA expression of tight junction proteins (occludin, claudin-1, ZO-1, and claudin-3) and redistribution of ZO-1 immunofluorescence. Further studies demonstrated that ZEN exposure activated the RhoA/ROCK signaling pathway, significantly up-regulated the mRNA expression of ROCK1, the main effector of the signaling pathway, the protein expression of phosphorylated myosin light chain (MLC) and myosin light chain kinase (MLCK), and relatively increased the activity of ATP in cells, simultaneously remodeling the cytoskeleton (F-actin). Overall, our study indicated that ZEN induced intestinal barrier dysfunction by activating the RhoA/ROCK signaling pathway. |
| first_indexed | 2024-03-09T20:05:51Z |
| format | Article |
| id | doaj.art-7aef2d15e0dc4641973b6c0e94e475b1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T20:05:51Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7aef2d15e0dc4641973b6c0e94e475b12023-11-24T00:33:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123201255010.3390/ijms232012550Zearalenone-Induced Mechanical Damage of Intestinal Barrier via the RhoA/ROCK Signaling Pathway in IPEC-J2 CellsBiying Huang0Jingjing Wang1Aixin Gu2Tianhu Wang3Jianping Li4Anshan Shan5Institute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, ChinaInstitute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, ChinaInstitute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, ChinaInstitute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, ChinaInstitute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, ChinaInstitute of Animal Nutrition, Northeast Agricultural University, Harbin 150030, ChinaZearalenone (ZEN) is a widespread contaminant of cereals and agricultural products which causes food safety issues. Ingesting food or feed contaminated with ZEN can disrupt the intestinal epithelial barrier function. The RhoA/ROCK signaling pathway plays a key role in regulating the epithelial barrier function, but studies on such roles have rarely focused on the intestine. The aim of this experiment was to investigate the exact mechanism of ZEN-induced intestinal barrier damage and whether the RhoA/ROCK signaling pathway is involved. The results showed that ZEN significantly induced alkaline phosphatase (AP) activity and FITC–dextran (4 kDa) passage across the epithelial barrier, which significantly reduced the transepithelial resistance (TEER). Meanwhile, ZEN could induce the significantly down-regulated mRNA expression of tight junction proteins (occludin, claudin-1, ZO-1, and claudin-3) and redistribution of ZO-1 immunofluorescence. Further studies demonstrated that ZEN exposure activated the RhoA/ROCK signaling pathway, significantly up-regulated the mRNA expression of ROCK1, the main effector of the signaling pathway, the protein expression of phosphorylated myosin light chain (MLC) and myosin light chain kinase (MLCK), and relatively increased the activity of ATP in cells, simultaneously remodeling the cytoskeleton (F-actin). Overall, our study indicated that ZEN induced intestinal barrier dysfunction by activating the RhoA/ROCK signaling pathway.https://www.mdpi.com/1422-0067/23/20/12550zearalenoneRhoA/ROCK pathwayintestinal barrierIPEC-J2 cells |
| spellingShingle | Biying Huang Jingjing Wang Aixin Gu Tianhu Wang Jianping Li Anshan Shan Zearalenone-Induced Mechanical Damage of Intestinal Barrier via the RhoA/ROCK Signaling Pathway in IPEC-J2 Cells International Journal of Molecular Sciences zearalenone RhoA/ROCK pathway intestinal barrier IPEC-J2 cells |
| title | Zearalenone-Induced Mechanical Damage of Intestinal Barrier via the RhoA/ROCK Signaling Pathway in IPEC-J2 Cells |
| title_full | Zearalenone-Induced Mechanical Damage of Intestinal Barrier via the RhoA/ROCK Signaling Pathway in IPEC-J2 Cells |
| title_fullStr | Zearalenone-Induced Mechanical Damage of Intestinal Barrier via the RhoA/ROCK Signaling Pathway in IPEC-J2 Cells |
| title_full_unstemmed | Zearalenone-Induced Mechanical Damage of Intestinal Barrier via the RhoA/ROCK Signaling Pathway in IPEC-J2 Cells |
| title_short | Zearalenone-Induced Mechanical Damage of Intestinal Barrier via the RhoA/ROCK Signaling Pathway in IPEC-J2 Cells |
| title_sort | zearalenone induced mechanical damage of intestinal barrier via the rhoa rock signaling pathway in ipec j2 cells |
| topic | zearalenone RhoA/ROCK pathway intestinal barrier IPEC-J2 cells |
| url | https://www.mdpi.com/1422-0067/23/20/12550 |
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