miR124a-3p inhibitor alleviates AFB1-induced hepatoxicity via targeting chicken glucocorticoid receptor mRNA
Glucocorticoid receptor (GR) plays crucial roles in various processes, including stress response, inflammatory response and toxin response, making it a therapeutic target for numerous diseases. microRNA (miRNA) can target and negatively regulate the expression of GR, thus interfering with its normal...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Poultry Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0032579125000781 |
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| author | Mindie Zhao Liang Chen Yulan Zhao Jie Liu Huimin Chen Ruqian Zhao |
| author_facet | Mindie Zhao Liang Chen Yulan Zhao Jie Liu Huimin Chen Ruqian Zhao |
| author_sort | Mindie Zhao |
| collection | DOAJ |
| description | Glucocorticoid receptor (GR) plays crucial roles in various processes, including stress response, inflammatory response and toxin response, making it a therapeutic target for numerous diseases. microRNA (miRNA) can target and negatively regulate the expression of GR, thus interfering with its normal function. Aflatoxin B1 (AFB1) seriously affects poultry health and productivity, exhibiting hepatotoxicity and cytotoxicity. However, the expression of GR and GR-targeting miRNAs in poultry after AFB1 poisoning has not been studied. In this study, four-day-old broiler chicks were randomly divided into control group (CON) and AFB1 group (AFB1). After a 3-day pre-feed, the AFB1 group was given 0.25 mg/kg of AFB1 for 18 days. Hematoxylin and eosin (HE) staining revealed AFB1-induced hepatocyte damage accompanied by inflammatory cell infiltration. Liver oxidative stress enzymes superoxide dismutase (SOD) and catalase (CAT) decreased significantly. RT-qPCR showed decreased mRNA expression of Phase I and II metabolic detoxification enzymes. Western blot analysis indicated reduced GR protein levels, while miRNA PCR revealed upregulation of GR-targeting miR-124a-3p, miR-142-3p, miR-18b-5p, and miR-183. After 24 h of 40 μM AFB1 treatment in LMH cells, Edu and flow cytometry confirmed inhibition of cell proliferation and promotion of apoptosis. Additionally, AFB1 induced oxidative stress and DNA damage. RT-qPCR showed reduced expression of certain Phase I/II metabolic detoxification enzymes and GR. Western blot confirmed a significant decrease in GR protein. miRNA PCR revealed upregulation of miR124a-3p. We found that transfection of LMH cells with miR124a-3p inhibitor alleviated the changes in GR and metabolic detoxification enzyme gene expression induced by AFB1. Additionally, AFB1-induced reductions in cell viability, increased apoptosis, inhibited proliferation, oxidative stress, and DNA damage were also alleviated. Overall, our findings suggest that inhibition of miR124a-3p, which targets GR, can ameliorate AFB1-induced hepatotoxicity. This study highlights GR and its miRNA as potential therapeutic targets for AFB1-induced liver disease, providing new insights into therapeutic strategies to mitigate the harmful effects of AFB1 exposure in poultry. |
| format | Article |
| id | doaj-art-343b955752924776aa6b92cac3cb5902 |
| institution | Kabale University |
| issn | 0032-5791 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Poultry Science |
| spelling | doaj-art-343b955752924776aa6b92cac3cb59022025-02-07T04:46:34ZengElsevierPoultry Science0032-57912025-03-011043104841miR124a-3p inhibitor alleviates AFB1-induced hepatoxicity via targeting chicken glucocorticoid receptor mRNAMindie Zhao0Liang Chen1Yulan Zhao2Jie Liu3Huimin Chen4Ruqian Zhao5National Key Laboratory of Meat Quality Control and Cultured Meat Development, Nanjing 210095, PR China; Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR ChinaNational Key Laboratory of Meat Quality Control and Cultured Meat Development, Nanjing 210095, PR China; Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR ChinaNational Key Laboratory of Meat Quality Control and Cultured Meat Development, Nanjing 210095, PR China; Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR ChinaNational Key Laboratory of Meat Quality Control and Cultured Meat Development, Nanjing 210095, PR China; Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR ChinaNational Key Laboratory of Meat Quality Control and Cultured Meat Development, Nanjing 210095, PR China; Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR ChinaNational Key Laboratory of Meat Quality Control and Cultured Meat Development, Nanjing 210095, PR China; Key Laboratory of Animal Physiology & Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, PR China; Corresponding author.Glucocorticoid receptor (GR) plays crucial roles in various processes, including stress response, inflammatory response and toxin response, making it a therapeutic target for numerous diseases. microRNA (miRNA) can target and negatively regulate the expression of GR, thus interfering with its normal function. Aflatoxin B1 (AFB1) seriously affects poultry health and productivity, exhibiting hepatotoxicity and cytotoxicity. However, the expression of GR and GR-targeting miRNAs in poultry after AFB1 poisoning has not been studied. In this study, four-day-old broiler chicks were randomly divided into control group (CON) and AFB1 group (AFB1). After a 3-day pre-feed, the AFB1 group was given 0.25 mg/kg of AFB1 for 18 days. Hematoxylin and eosin (HE) staining revealed AFB1-induced hepatocyte damage accompanied by inflammatory cell infiltration. Liver oxidative stress enzymes superoxide dismutase (SOD) and catalase (CAT) decreased significantly. RT-qPCR showed decreased mRNA expression of Phase I and II metabolic detoxification enzymes. Western blot analysis indicated reduced GR protein levels, while miRNA PCR revealed upregulation of GR-targeting miR-124a-3p, miR-142-3p, miR-18b-5p, and miR-183. After 24 h of 40 μM AFB1 treatment in LMH cells, Edu and flow cytometry confirmed inhibition of cell proliferation and promotion of apoptosis. Additionally, AFB1 induced oxidative stress and DNA damage. RT-qPCR showed reduced expression of certain Phase I/II metabolic detoxification enzymes and GR. Western blot confirmed a significant decrease in GR protein. miRNA PCR revealed upregulation of miR124a-3p. We found that transfection of LMH cells with miR124a-3p inhibitor alleviated the changes in GR and metabolic detoxification enzyme gene expression induced by AFB1. Additionally, AFB1-induced reductions in cell viability, increased apoptosis, inhibited proliferation, oxidative stress, and DNA damage were also alleviated. Overall, our findings suggest that inhibition of miR124a-3p, which targets GR, can ameliorate AFB1-induced hepatotoxicity. This study highlights GR and its miRNA as potential therapeutic targets for AFB1-induced liver disease, providing new insights into therapeutic strategies to mitigate the harmful effects of AFB1 exposure in poultry.http://www.sciencedirect.com/science/article/pii/S0032579125000781AFB1LMHcytotoxicityGlucocorticoid receptormicroRNA |
| spellingShingle | Mindie Zhao Liang Chen Yulan Zhao Jie Liu Huimin Chen Ruqian Zhao miR124a-3p inhibitor alleviates AFB1-induced hepatoxicity via targeting chicken glucocorticoid receptor mRNA Poultry Science AFB1 LMH cytotoxicity Glucocorticoid receptor microRNA |
| title | miR124a-3p inhibitor alleviates AFB1-induced hepatoxicity via targeting chicken glucocorticoid receptor mRNA |
| title_full | miR124a-3p inhibitor alleviates AFB1-induced hepatoxicity via targeting chicken glucocorticoid receptor mRNA |
| title_fullStr | miR124a-3p inhibitor alleviates AFB1-induced hepatoxicity via targeting chicken glucocorticoid receptor mRNA |
| title_full_unstemmed | miR124a-3p inhibitor alleviates AFB1-induced hepatoxicity via targeting chicken glucocorticoid receptor mRNA |
| title_short | miR124a-3p inhibitor alleviates AFB1-induced hepatoxicity via targeting chicken glucocorticoid receptor mRNA |
| title_sort | mir124a 3p inhibitor alleviates afb1 induced hepatoxicity via targeting chicken glucocorticoid receptor mrna |
| topic | AFB1 LMH cytotoxicity Glucocorticoid receptor microRNA |
| url | http://www.sciencedirect.com/science/article/pii/S0032579125000781 |
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