miR-210 in Exosomes Derived from Macrophages under High Glucose Promotes Mouse Diabetic Obesity Pathogenesis by Suppressing NDUFA4 Expression
Objective. Type 2 diabetes mellitus (T2DM) is featured by insulin resistance and lipid metabolism dysregulation. A large number of miRNAs were identified in exosomes derived from adipose tissue macrophages associated with T2DM pathogenesis, but its pathogenic roles remain unknown. This study is aime...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2020/6894684 |
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| author | Feng Tian Ping Tang Zhilian Sun Ruifen Zhang Danhua Zhu Junying He Jixing Liao Qinghua Wan Jie Shen |
| author_facet | Feng Tian Ping Tang Zhilian Sun Ruifen Zhang Danhua Zhu Junying He Jixing Liao Qinghua Wan Jie Shen |
| author_sort | Feng Tian |
| collection | DOAJ |
| description | Objective. Type 2 diabetes mellitus (T2DM) is featured by insulin resistance and lipid metabolism dysregulation. A large number of miRNAs were identified in exosomes derived from adipose tissue macrophages associated with T2DM pathogenesis, but its pathogenic roles remain unknown. This study is aimed at investigating the function of miR-210 in diabetic obesity. Methods. Exosomes from mouse macrophage RAW264.7 cells were characterized by electron microscopy, combined with biomarker expression by western blot. Expression of miR-210 was determined by quantitative RT-PCR. Glucose uptake was measured by a fluorometric method, and the mitochondrial respiratory chain activity was evaluated by ELISA. The target gene of miR-210 was validated by dual-luciferase reporter and pull-down assays. A mouse obese diabetic model was established by a high-fat diet and streptozocin treatment. Results. miR-210 was highly expressed in exosomes derived from high glucose-induced macrophage RAW264.7 cells. Macrophage-derived exosomes impaired glucose uptake and mitochondrial CIV complex activity and suppressed NADH dehydrogenase ubiquinone 1 alpha subcomplex 4 (NDUFA4) expression in 3T3-L1 adipocytes. miR-210 directly bind with mRNA sequences of NDUFA4 gene. Inhibition of miR-210 mitigated the effects of macrophage-derived exosomes on the glucose uptake and complex IV (CIV) activity in 3T3-L1 adipocytes, and NDUFA4 overexpression offset the inhibition of glucose uptake and CIV activity by macrophage-derived exosomes. Furthermore, mice with miR-210 knockout showed greatly repressed diabetic obesity development. Conclusion. miR-210 derived from adipose tissue macrophages promotes mouse obese diabetes pathogenesis by regulating glucose uptake and mitochondrial CIV activity through targeting NDUFA4 gene expression. |
| format | Article |
| id | doaj-art-9bbac28f831f4fcdbb2adb167d72eed0 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-9bbac28f831f4fcdbb2adb167d72eed02025-02-03T01:28:21ZengWileyJournal of Diabetes Research2314-67452314-67532020-01-01202010.1155/2020/68946846894684miR-210 in Exosomes Derived from Macrophages under High Glucose Promotes Mouse Diabetic Obesity Pathogenesis by Suppressing NDUFA4 ExpressionFeng Tian0Ping Tang1Zhilian Sun2Ruifen Zhang3Danhua Zhu4Junying He5Jixing Liao6Qinghua Wan7Jie Shen8Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, ChinaDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, ChinaDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, ChinaDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, ChinaDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, ChinaDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, ChinaDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, ChinaDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, ChinaDepartment of Endocrinology and Metabolism, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, ChinaObjective. Type 2 diabetes mellitus (T2DM) is featured by insulin resistance and lipid metabolism dysregulation. A large number of miRNAs were identified in exosomes derived from adipose tissue macrophages associated with T2DM pathogenesis, but its pathogenic roles remain unknown. This study is aimed at investigating the function of miR-210 in diabetic obesity. Methods. Exosomes from mouse macrophage RAW264.7 cells were characterized by electron microscopy, combined with biomarker expression by western blot. Expression of miR-210 was determined by quantitative RT-PCR. Glucose uptake was measured by a fluorometric method, and the mitochondrial respiratory chain activity was evaluated by ELISA. The target gene of miR-210 was validated by dual-luciferase reporter and pull-down assays. A mouse obese diabetic model was established by a high-fat diet and streptozocin treatment. Results. miR-210 was highly expressed in exosomes derived from high glucose-induced macrophage RAW264.7 cells. Macrophage-derived exosomes impaired glucose uptake and mitochondrial CIV complex activity and suppressed NADH dehydrogenase ubiquinone 1 alpha subcomplex 4 (NDUFA4) expression in 3T3-L1 adipocytes. miR-210 directly bind with mRNA sequences of NDUFA4 gene. Inhibition of miR-210 mitigated the effects of macrophage-derived exosomes on the glucose uptake and complex IV (CIV) activity in 3T3-L1 adipocytes, and NDUFA4 overexpression offset the inhibition of glucose uptake and CIV activity by macrophage-derived exosomes. Furthermore, mice with miR-210 knockout showed greatly repressed diabetic obesity development. Conclusion. miR-210 derived from adipose tissue macrophages promotes mouse obese diabetes pathogenesis by regulating glucose uptake and mitochondrial CIV activity through targeting NDUFA4 gene expression.http://dx.doi.org/10.1155/2020/6894684 |
| spellingShingle | Feng Tian Ping Tang Zhilian Sun Ruifen Zhang Danhua Zhu Junying He Jixing Liao Qinghua Wan Jie Shen miR-210 in Exosomes Derived from Macrophages under High Glucose Promotes Mouse Diabetic Obesity Pathogenesis by Suppressing NDUFA4 Expression Journal of Diabetes Research |
| title | miR-210 in Exosomes Derived from Macrophages under High Glucose Promotes Mouse Diabetic Obesity Pathogenesis by Suppressing NDUFA4 Expression |
| title_full | miR-210 in Exosomes Derived from Macrophages under High Glucose Promotes Mouse Diabetic Obesity Pathogenesis by Suppressing NDUFA4 Expression |
| title_fullStr | miR-210 in Exosomes Derived from Macrophages under High Glucose Promotes Mouse Diabetic Obesity Pathogenesis by Suppressing NDUFA4 Expression |
| title_full_unstemmed | miR-210 in Exosomes Derived from Macrophages under High Glucose Promotes Mouse Diabetic Obesity Pathogenesis by Suppressing NDUFA4 Expression |
| title_short | miR-210 in Exosomes Derived from Macrophages under High Glucose Promotes Mouse Diabetic Obesity Pathogenesis by Suppressing NDUFA4 Expression |
| title_sort | mir 210 in exosomes derived from macrophages under high glucose promotes mouse diabetic obesity pathogenesis by suppressing ndufa4 expression |
| url | http://dx.doi.org/10.1155/2020/6894684 |
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