Chronic Variable Stress Induces Hepatic Fe(II) Deposition by Up-Regulating ZIP14 Expression via miR-181 Family Pathway in Rats

It is well-known that hepatic iron dysregulation, which is harmful to health, can be caused by stress. The aim of the study was to evaluate chronic variable stress (CVS) on liver damage, hepatic ferrous iron deposition and its molecular regulatory mechanism in rats. Sprague Dawley rats at seven week...

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Main Authors: Shuxia Jiang, Taining Guo, Shihui Guo, Jiang Gao, Yingdong Ni, Wenqiang Ma, Ruqian Zhao
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Biology
Subjects:
Online Access:https://www.mdpi.com/2079-7737/10/7/653
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author Shuxia Jiang
Taining Guo
Shihui Guo
Jiang Gao
Yingdong Ni
Wenqiang Ma
Ruqian Zhao
author_facet Shuxia Jiang
Taining Guo
Shihui Guo
Jiang Gao
Yingdong Ni
Wenqiang Ma
Ruqian Zhao
author_sort Shuxia Jiang
collection DOAJ
description It is well-known that hepatic iron dysregulation, which is harmful to health, can be caused by stress. The aim of the study was to evaluate chronic variable stress (CVS) on liver damage, hepatic ferrous iron deposition and its molecular regulatory mechanism in rats. Sprague Dawley rats at seven weeks of age were randomly divided into two groups: a control group (Con) and a CVS group. CVS reduces body weight, but increases the liver-to-body weight ratio. The exposure of rats to CVS increased plasma aspartate aminotransferase (AST), alkaline phosphatase (ALP) and hepatic malondialdehyde (MDA) levels, but decreased glutathione peroxidase (GSH-Px) activity, resulting in liver damage. CVS lowered the total amount of hepatic iron content, but induced hepatic Fe(II) accumulation. CVS up-regulated the expression of transferrin receptor 1 (TFR1) and ZRT/IRT-like protein 14 (ZIP14), but down-regulated ferritin and miR-181 family members. In addition, miR-181 family expression was found to regulate ZIP14 expression in HEK-293T cells by the dual-luciferase reporter system. These results indicate that CVS results in liver damage and induces hepatic Fe(II) accumulation, which is closely associated with the up-regulation of ZIP14 expression via the miR-181 family pathway.
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spelling doaj.art-19202efcc80843b09175b423f30a8f092023-11-22T03:15:59ZengMDPI AGBiology2079-77372021-07-0110765310.3390/biology10070653Chronic Variable Stress Induces Hepatic Fe(II) Deposition by Up-Regulating ZIP14 Expression via miR-181 Family Pathway in RatsShuxia Jiang0Taining Guo1Shihui Guo2Jiang Gao3Yingdong Ni4Wenqiang Ma5Ruqian Zhao6Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaKey Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaKey Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaKey Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaKey Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaKey Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaKey Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, ChinaIt is well-known that hepatic iron dysregulation, which is harmful to health, can be caused by stress. The aim of the study was to evaluate chronic variable stress (CVS) on liver damage, hepatic ferrous iron deposition and its molecular regulatory mechanism in rats. Sprague Dawley rats at seven weeks of age were randomly divided into two groups: a control group (Con) and a CVS group. CVS reduces body weight, but increases the liver-to-body weight ratio. The exposure of rats to CVS increased plasma aspartate aminotransferase (AST), alkaline phosphatase (ALP) and hepatic malondialdehyde (MDA) levels, but decreased glutathione peroxidase (GSH-Px) activity, resulting in liver damage. CVS lowered the total amount of hepatic iron content, but induced hepatic Fe(II) accumulation. CVS up-regulated the expression of transferrin receptor 1 (TFR1) and ZRT/IRT-like protein 14 (ZIP14), but down-regulated ferritin and miR-181 family members. In addition, miR-181 family expression was found to regulate ZIP14 expression in HEK-293T cells by the dual-luciferase reporter system. These results indicate that CVS results in liver damage and induces hepatic Fe(II) accumulation, which is closely associated with the up-regulation of ZIP14 expression via the miR-181 family pathway.https://www.mdpi.com/2079-7737/10/7/653chronic variable stresshepatic Fe(II)ZIP14miR-181rats
spellingShingle Shuxia Jiang
Taining Guo
Shihui Guo
Jiang Gao
Yingdong Ni
Wenqiang Ma
Ruqian Zhao
Chronic Variable Stress Induces Hepatic Fe(II) Deposition by Up-Regulating ZIP14 Expression via miR-181 Family Pathway in Rats
Biology
chronic variable stress
hepatic Fe(II)
ZIP14
miR-181
rats
title Chronic Variable Stress Induces Hepatic Fe(II) Deposition by Up-Regulating ZIP14 Expression via miR-181 Family Pathway in Rats
title_full Chronic Variable Stress Induces Hepatic Fe(II) Deposition by Up-Regulating ZIP14 Expression via miR-181 Family Pathway in Rats
title_fullStr Chronic Variable Stress Induces Hepatic Fe(II) Deposition by Up-Regulating ZIP14 Expression via miR-181 Family Pathway in Rats
title_full_unstemmed Chronic Variable Stress Induces Hepatic Fe(II) Deposition by Up-Regulating ZIP14 Expression via miR-181 Family Pathway in Rats
title_short Chronic Variable Stress Induces Hepatic Fe(II) Deposition by Up-Regulating ZIP14 Expression via miR-181 Family Pathway in Rats
title_sort chronic variable stress induces hepatic fe ii deposition by up regulating zip14 expression via mir 181 family pathway in rats
topic chronic variable stress
hepatic Fe(II)
ZIP14
miR-181
rats
url https://www.mdpi.com/2079-7737/10/7/653
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