Microvesicle-Shuttled microRNA-130b Activates the Hepatic Inflammation by Inhibiting Glucocorticoid-Receptor-Mediated Immunosuppression in High-Fat Diet-Induced Obese Mice
Metabolism-disorder-induced liver diseases have become increasingly prevalent worldwide and are clinically linked to obesity and type 2 diabetes. In addition, a large number of previous literature studies have indicated that plasma miR-130b is a promising biomarker for the early diagnosis and treatm...
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MDPI AG
2024-11-01
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| Series: | Veterinary Sciences |
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| Online Access: | https://www.mdpi.com/2306-7381/11/11/565 |
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| author | Zhengqiang Han Lijun Wang Shiyong Xu Horsen Zhang Ji Cheng Shifeng Pan |
| author_facet | Zhengqiang Han Lijun Wang Shiyong Xu Horsen Zhang Ji Cheng Shifeng Pan |
| author_sort | Zhengqiang Han |
| collection | DOAJ |
| description | Metabolism-disorder-induced liver diseases have become increasingly prevalent worldwide and are clinically linked to obesity and type 2 diabetes. In addition, a large number of previous literature studies have indicated that plasma miR-130b is a promising biomarker for the early diagnosis and treatment of obesity. However, whether miRNA-130b that was positively correlated with obesity resulted in hepatic inflammation needs to be further studied. Therefore, the study aims to determine the effect of microvesicle-shuttled miRNA-130b (miR-130b-MV) on the hepatic inflammation and its potential mechanism in high-fat diet-induced obese mice. Three-week-old C57BL/6 mice were fed a high-fat diet for eight weeks. Then, the obese mice received tail vein injections of MV-packaged scrambled control microRNA (miR-SC-MV) or miR-130b-MV every other day for 10 days. Compared with the control group, the miR-130b-MV injection significantly reduced the body weight while increasing the ratio of liver wet weight to total body weight. In addition, the miR-130b-MV injection significantly activated the hepatic inflammation by increasing the expression of proinflammatory genes, although the plasma concentrations of IL-6 and TNF-α were only slightly increased. Furthermore, the miR-130b-MV injection significantly increased the hepatic miR-130b expression while significantly suppressing the protein expression and phosphorylation of GR, a potential target of miR-130b. Moreover, the miR-130b overexpression results in a decrease in the expression of endogenous GR protein and a decrease in the activity of the luciferase reporter of GR 3′-UTR. In addition, the miR-130b-MV injection significantly upregulated NF-kB (p50) in both the cytoplasm and nucleus, showing enhanced proinflammation response. The above results demonstrated that miR-130b-MV activated the hepatic inflammation by inhibiting GR-mediated immunosuppression in high-fat diet-induced obese mice, suggesting a novel mechanism underlying the obesity-induced hepatic inflammation, and the inhibition of miR-130b may serve as a new molecular therapeutic target for the prevention and treatment of hepatic inflammation. |
| format | Article |
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| institution | OA Journals |
| issn | 2306-7381 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Veterinary Sciences |
| spelling | doaj-art-4e5f9cd5a6854c0f825d02cc637a778b2025-08-20T02:04:43ZengMDPI AGVeterinary Sciences2306-73812024-11-01111156510.3390/vetsci11110565Microvesicle-Shuttled microRNA-130b Activates the Hepatic Inflammation by Inhibiting Glucocorticoid-Receptor-Mediated Immunosuppression in High-Fat Diet-Induced Obese MiceZhengqiang Han0Lijun Wang1Shiyong Xu2Horsen Zhang3Ji Cheng4Shifeng Pan5College of Animal Science and Food Engineering, Jinling Institute of Technology, Nanjing 210038, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaCollege of Animal Science and Food Engineering, Jinling Institute of Technology, Nanjing 210038, ChinaLesaffre (Mingguang) Co., Ltd., Chuzhou 239000, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaCollege of Veterinary Medicine, Yangzhou University, Yangzhou 225009, ChinaMetabolism-disorder-induced liver diseases have become increasingly prevalent worldwide and are clinically linked to obesity and type 2 diabetes. In addition, a large number of previous literature studies have indicated that plasma miR-130b is a promising biomarker for the early diagnosis and treatment of obesity. However, whether miRNA-130b that was positively correlated with obesity resulted in hepatic inflammation needs to be further studied. Therefore, the study aims to determine the effect of microvesicle-shuttled miRNA-130b (miR-130b-MV) on the hepatic inflammation and its potential mechanism in high-fat diet-induced obese mice. Three-week-old C57BL/6 mice were fed a high-fat diet for eight weeks. Then, the obese mice received tail vein injections of MV-packaged scrambled control microRNA (miR-SC-MV) or miR-130b-MV every other day for 10 days. Compared with the control group, the miR-130b-MV injection significantly reduced the body weight while increasing the ratio of liver wet weight to total body weight. In addition, the miR-130b-MV injection significantly activated the hepatic inflammation by increasing the expression of proinflammatory genes, although the plasma concentrations of IL-6 and TNF-α were only slightly increased. Furthermore, the miR-130b-MV injection significantly increased the hepatic miR-130b expression while significantly suppressing the protein expression and phosphorylation of GR, a potential target of miR-130b. Moreover, the miR-130b overexpression results in a decrease in the expression of endogenous GR protein and a decrease in the activity of the luciferase reporter of GR 3′-UTR. In addition, the miR-130b-MV injection significantly upregulated NF-kB (p50) in both the cytoplasm and nucleus, showing enhanced proinflammation response. The above results demonstrated that miR-130b-MV activated the hepatic inflammation by inhibiting GR-mediated immunosuppression in high-fat diet-induced obese mice, suggesting a novel mechanism underlying the obesity-induced hepatic inflammation, and the inhibition of miR-130b may serve as a new molecular therapeutic target for the prevention and treatment of hepatic inflammation.https://www.mdpi.com/2306-7381/11/11/565microvesiclesmiRNA-130bhepatic inflammationGR-mediated immunosuppressionhigh-fat diet-induced obese mice |
| spellingShingle | Zhengqiang Han Lijun Wang Shiyong Xu Horsen Zhang Ji Cheng Shifeng Pan Microvesicle-Shuttled microRNA-130b Activates the Hepatic Inflammation by Inhibiting Glucocorticoid-Receptor-Mediated Immunosuppression in High-Fat Diet-Induced Obese Mice Veterinary Sciences microvesicles miRNA-130b hepatic inflammation GR-mediated immunosuppression high-fat diet-induced obese mice |
| title | Microvesicle-Shuttled microRNA-130b Activates the Hepatic Inflammation by Inhibiting Glucocorticoid-Receptor-Mediated Immunosuppression in High-Fat Diet-Induced Obese Mice |
| title_full | Microvesicle-Shuttled microRNA-130b Activates the Hepatic Inflammation by Inhibiting Glucocorticoid-Receptor-Mediated Immunosuppression in High-Fat Diet-Induced Obese Mice |
| title_fullStr | Microvesicle-Shuttled microRNA-130b Activates the Hepatic Inflammation by Inhibiting Glucocorticoid-Receptor-Mediated Immunosuppression in High-Fat Diet-Induced Obese Mice |
| title_full_unstemmed | Microvesicle-Shuttled microRNA-130b Activates the Hepatic Inflammation by Inhibiting Glucocorticoid-Receptor-Mediated Immunosuppression in High-Fat Diet-Induced Obese Mice |
| title_short | Microvesicle-Shuttled microRNA-130b Activates the Hepatic Inflammation by Inhibiting Glucocorticoid-Receptor-Mediated Immunosuppression in High-Fat Diet-Induced Obese Mice |
| title_sort | microvesicle shuttled microrna 130b activates the hepatic inflammation by inhibiting glucocorticoid receptor mediated immunosuppression in high fat diet induced obese mice |
| topic | microvesicles miRNA-130b hepatic inflammation GR-mediated immunosuppression high-fat diet-induced obese mice |
| url | https://www.mdpi.com/2306-7381/11/11/565 |
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