The Protective Effects of Lactoferrin on Aflatoxin M1-Induced Compromised Intestinal Integrity
Aflatoxin M1 (AFM1), the only toxin with maximum residue levels in milk, has adverse effects on the intestinal barrier, resulting in intestinal inflammatory disease. Lactoferrin (LF), one of the important bioactive proteins in milk, performs multiple biological functions, but knowledge of the protec...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/1/289 |
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| author | Ya-Nan Gao Song-Li Li Xue Yang Jia-Qi Wang Nan Zheng |
| author_facet | Ya-Nan Gao Song-Li Li Xue Yang Jia-Qi Wang Nan Zheng |
| author_sort | Ya-Nan Gao |
| collection | DOAJ |
| description | Aflatoxin M1 (AFM1), the only toxin with maximum residue levels in milk, has adverse effects on the intestinal barrier, resulting in intestinal inflammatory disease. Lactoferrin (LF), one of the important bioactive proteins in milk, performs multiple biological functions, but knowledge of the protective effects of LF on the compromised intestinal barrier induced by AFM1 has not been investigated. In the present study, results using Balb/C mice and differentiated Caco-2 cells showed that LF intervention decreased AFM1-induced increased intestinal permeability, improved the protein expression of claudin-3, occludin and ZO-1, and repaired the injured intestinal barrier. The transcriptome and proteome were used to clarify the underlying mechanisms. It was found that LF reduced the intestinal barrier dysfunction caused by AFM1 and was associated with intestinal cell survival related pathways, such as cell cycle, apoptosis and MAPK signaling pathway and intestinal integrity related pathways including endocytosis, tight junction, adherens junction and gap junction. The cross-omics analysis suggested that insulin receptor (INSR), cytoplasmic FMR1 interacting protein 2 (CYFIP2), dedicator of cytokinesis 1 (DOCK1) and ribonucleotide reductase regulatory subunit M2 (RRM2) were the potential key regulators as LF repaired the compromised intestinal barrier. These findings indicated that LF may be an alternative treatment for the compromised intestinal barrier induced by AFM1. |
| first_indexed | 2024-03-10T03:38:53Z |
| format | Article |
| id | doaj.art-a02ab0ac91b4462b94eed90ec46a2ccb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:38:53Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a02ab0ac91b4462b94eed90ec46a2ccb2023-11-23T11:37:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0123128910.3390/ijms23010289The Protective Effects of Lactoferrin on Aflatoxin M1-Induced Compromised Intestinal IntegrityYa-Nan Gao0Song-Li Li1Xue Yang2Jia-Qi Wang3Nan Zheng4Key Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaKey Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaKey Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaKey Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaKey Laboratory of Quality & Safety Control for Milk and Dairy Products of Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaAflatoxin M1 (AFM1), the only toxin with maximum residue levels in milk, has adverse effects on the intestinal barrier, resulting in intestinal inflammatory disease. Lactoferrin (LF), one of the important bioactive proteins in milk, performs multiple biological functions, but knowledge of the protective effects of LF on the compromised intestinal barrier induced by AFM1 has not been investigated. In the present study, results using Balb/C mice and differentiated Caco-2 cells showed that LF intervention decreased AFM1-induced increased intestinal permeability, improved the protein expression of claudin-3, occludin and ZO-1, and repaired the injured intestinal barrier. The transcriptome and proteome were used to clarify the underlying mechanisms. It was found that LF reduced the intestinal barrier dysfunction caused by AFM1 and was associated with intestinal cell survival related pathways, such as cell cycle, apoptosis and MAPK signaling pathway and intestinal integrity related pathways including endocytosis, tight junction, adherens junction and gap junction. The cross-omics analysis suggested that insulin receptor (INSR), cytoplasmic FMR1 interacting protein 2 (CYFIP2), dedicator of cytokinesis 1 (DOCK1) and ribonucleotide reductase regulatory subunit M2 (RRM2) were the potential key regulators as LF repaired the compromised intestinal barrier. These findings indicated that LF may be an alternative treatment for the compromised intestinal barrier induced by AFM1.https://www.mdpi.com/1422-0067/23/1/289aflatoxin M1lactoferrinintestinal barriertight junctiontranscriptomeproteome |
| spellingShingle | Ya-Nan Gao Song-Li Li Xue Yang Jia-Qi Wang Nan Zheng The Protective Effects of Lactoferrin on Aflatoxin M1-Induced Compromised Intestinal Integrity International Journal of Molecular Sciences aflatoxin M1 lactoferrin intestinal barrier tight junction transcriptome proteome |
| title | The Protective Effects of Lactoferrin on Aflatoxin M1-Induced Compromised Intestinal Integrity |
| title_full | The Protective Effects of Lactoferrin on Aflatoxin M1-Induced Compromised Intestinal Integrity |
| title_fullStr | The Protective Effects of Lactoferrin on Aflatoxin M1-Induced Compromised Intestinal Integrity |
| title_full_unstemmed | The Protective Effects of Lactoferrin on Aflatoxin M1-Induced Compromised Intestinal Integrity |
| title_short | The Protective Effects of Lactoferrin on Aflatoxin M1-Induced Compromised Intestinal Integrity |
| title_sort | protective effects of lactoferrin on aflatoxin m1 induced compromised intestinal integrity |
| topic | aflatoxin M1 lactoferrin intestinal barrier tight junction transcriptome proteome |
| url | https://www.mdpi.com/1422-0067/23/1/289 |
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