Inhibition of miR-146a-5p and miR-8114 in Insulin-Secreting Cells Contributes to the Protection of Melatonin against Stearic Acid-Induced Cellular Senescence by Targeting Mafa
Background Chronic exposure to elevated levels of saturated fatty acids results in pancreatic β-cell senescence. However, targets and effective agents for preventing stearic acid-induced β-cell senescence are still lacking. Although melatonin administration can protect β-cells against lipotoxicity t...
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| Format: | Article |
| Language: | English |
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Korean Endocrine Society
2022-12-01
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| Series: | Endocrinology and Metabolism |
| Subjects: | |
| Online Access: | http://www.e-enm.org/upload/pdf/enm-2022-1565.pdf |
| _version_ | 1797962265623789568 |
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| author | Shenghan Su Qingrui Zhao Lingfeng Dan Yuqing Lin Xuebei Li Yunjin Zhang Chunxiao Yang Yimeng Dong Xiaohan Li Romano Regazzi Changhao Sun Xia Chu Huimin Lu |
| author_facet | Shenghan Su Qingrui Zhao Lingfeng Dan Yuqing Lin Xuebei Li Yunjin Zhang Chunxiao Yang Yimeng Dong Xiaohan Li Romano Regazzi Changhao Sun Xia Chu Huimin Lu |
| author_sort | Shenghan Su |
| collection | DOAJ |
| description | Background Chronic exposure to elevated levels of saturated fatty acids results in pancreatic β-cell senescence. However, targets and effective agents for preventing stearic acid-induced β-cell senescence are still lacking. Although melatonin administration can protect β-cells against lipotoxicity through anti-senescence processes, the precise underlying mechanisms still need to be explored. Therefore, we investigated the anti-senescence effect of melatonin on stearic acid-treated mouse β-cells and elucidated the possible role of microRNAs in this process. Methods β-Cell senescence was identified by measuring the expression of senescence-related genes and senescence-associated β-galactosidase staining. Gain- and loss-of-function approaches were used to investigate the involvement of microRNAs in stearic acid-evoked β-cell senescence and dysfunction. Bioinformatics analyses and luciferase reporter activity assays were applied to predict the direct targets of microRNAs. Results Long-term exposure to a high concentration of stearic acid-induced senescence and upregulated miR-146a-5p and miR-8114 expression in both mouse islets and β-TC6 cell lines. Melatonin effectively suppressed this process and reduced the levels of these two miRNAs. A remarkable reversibility of stearic acid-induced β-cell senescence and dysfunction was observed after silencing miR-146a-5p and miR-8114. Moreover, V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) was verified as a direct target of miR-146a-5p and miR-8114. Melatonin also significantly ameliorated senescence and dysfunction in miR-146a-5pand miR-8114-transfected β-cells. Conclusion These data demonstrate that melatonin protects against stearic acid-induced β-cell senescence by inhibiting miR-146a- 5p and miR-8114 and upregulating Mafa expression. This not only provides novel targets for preventing stearic acid-induced β-cell dysfunction, but also points to melatonin as a promising drug to combat type 2 diabetes progression. |
| first_indexed | 2024-04-11T01:10:39Z |
| format | Article |
| id | doaj.art-43f2ab12ea28493e85d44c7ad8de5ad1 |
| institution | Directory Open Access Journal |
| issn | 2093-596X 2093-5978 |
| language | English |
| last_indexed | 2024-04-11T01:10:39Z |
| publishDate | 2022-12-01 |
| publisher | Korean Endocrine Society |
| record_format | Article |
| series | Endocrinology and Metabolism |
| spelling | doaj.art-43f2ab12ea28493e85d44c7ad8de5ad12023-01-04T05:41:52ZengKorean Endocrine SocietyEndocrinology and Metabolism2093-596X2093-59782022-12-0137690191710.3803/EnM.2022.15652353Inhibition of miR-146a-5p and miR-8114 in Insulin-Secreting Cells Contributes to the Protection of Melatonin against Stearic Acid-Induced Cellular Senescence by Targeting MafaShenghan Su0Qingrui Zhao1Lingfeng Dan2Yuqing Lin3Xuebei Li4Yunjin Zhang5Chunxiao Yang6Yimeng Dong7Xiaohan Li8Romano Regazzi9Changhao Sun10Xia Chu11Huimin Lu12 Department of Nutrition and Food Hygiene (National Key Discipline), Public Health College, Harbin Medical University, Harbin, China Department of Nutrition and Food Hygiene (National Key Discipline), Public Health College, Harbin Medical University, Harbin, China Department of Nutrition and Food Hygiene (National Key Discipline), Public Health College, Harbin Medical University, Harbin, China Department of Nutrition and Food Hygiene (National Key Discipline), Public Health College, Harbin Medical University, Harbin, China Department of Nutrition and Food Hygiene (National Key Discipline), Public Health College, Harbin Medical University, Harbin, China Department of Nutrition and Food Hygiene (National Key Discipline), Public Health College, Harbin Medical University, Harbin, China Department of Nutrition and Food Hygiene (National Key Discipline), Public Health College, Harbin Medical University, Harbin, China Department of Nutrition and Food Hygiene (National Key Discipline), Public Health College, Harbin Medical University, Harbin, China Department of Nutrition and Food Hygiene (National Key Discipline), Public Health College, Harbin Medical University, Harbin, China Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland Department of Nutrition and Food Hygiene (National Key Discipline), Public Health College, Harbin Medical University, Harbin, China Department of Nutrition and Food Hygiene (National Key Discipline), Public Health College, Harbin Medical University, Harbin, China Department of Nutrition and Food Hygiene (National Key Discipline), Public Health College, Harbin Medical University, Harbin, ChinaBackground Chronic exposure to elevated levels of saturated fatty acids results in pancreatic β-cell senescence. However, targets and effective agents for preventing stearic acid-induced β-cell senescence are still lacking. Although melatonin administration can protect β-cells against lipotoxicity through anti-senescence processes, the precise underlying mechanisms still need to be explored. Therefore, we investigated the anti-senescence effect of melatonin on stearic acid-treated mouse β-cells and elucidated the possible role of microRNAs in this process. Methods β-Cell senescence was identified by measuring the expression of senescence-related genes and senescence-associated β-galactosidase staining. Gain- and loss-of-function approaches were used to investigate the involvement of microRNAs in stearic acid-evoked β-cell senescence and dysfunction. Bioinformatics analyses and luciferase reporter activity assays were applied to predict the direct targets of microRNAs. Results Long-term exposure to a high concentration of stearic acid-induced senescence and upregulated miR-146a-5p and miR-8114 expression in both mouse islets and β-TC6 cell lines. Melatonin effectively suppressed this process and reduced the levels of these two miRNAs. A remarkable reversibility of stearic acid-induced β-cell senescence and dysfunction was observed after silencing miR-146a-5p and miR-8114. Moreover, V-maf musculoaponeurotic fibrosarcoma oncogene homolog A (Mafa) was verified as a direct target of miR-146a-5p and miR-8114. Melatonin also significantly ameliorated senescence and dysfunction in miR-146a-5pand miR-8114-transfected β-cells. Conclusion These data demonstrate that melatonin protects against stearic acid-induced β-cell senescence by inhibiting miR-146a- 5p and miR-8114 and upregulating Mafa expression. This not only provides novel targets for preventing stearic acid-induced β-cell dysfunction, but also points to melatonin as a promising drug to combat type 2 diabetes progression.http://www.e-enm.org/upload/pdf/enm-2022-1565.pdfstearic acidmelatoninmicrornascellular senescencemafa |
| spellingShingle | Shenghan Su Qingrui Zhao Lingfeng Dan Yuqing Lin Xuebei Li Yunjin Zhang Chunxiao Yang Yimeng Dong Xiaohan Li Romano Regazzi Changhao Sun Xia Chu Huimin Lu Inhibition of miR-146a-5p and miR-8114 in Insulin-Secreting Cells Contributes to the Protection of Melatonin against Stearic Acid-Induced Cellular Senescence by Targeting Mafa Endocrinology and Metabolism stearic acid melatonin micrornas cellular senescence mafa |
| title | Inhibition of miR-146a-5p and miR-8114 in Insulin-Secreting Cells Contributes to the Protection of Melatonin against Stearic Acid-Induced Cellular Senescence by Targeting Mafa |
| title_full | Inhibition of miR-146a-5p and miR-8114 in Insulin-Secreting Cells Contributes to the Protection of Melatonin against Stearic Acid-Induced Cellular Senescence by Targeting Mafa |
| title_fullStr | Inhibition of miR-146a-5p and miR-8114 in Insulin-Secreting Cells Contributes to the Protection of Melatonin against Stearic Acid-Induced Cellular Senescence by Targeting Mafa |
| title_full_unstemmed | Inhibition of miR-146a-5p and miR-8114 in Insulin-Secreting Cells Contributes to the Protection of Melatonin against Stearic Acid-Induced Cellular Senescence by Targeting Mafa |
| title_short | Inhibition of miR-146a-5p and miR-8114 in Insulin-Secreting Cells Contributes to the Protection of Melatonin against Stearic Acid-Induced Cellular Senescence by Targeting Mafa |
| title_sort | inhibition of mir 146a 5p and mir 8114 in insulin secreting cells contributes to the protection of melatonin against stearic acid induced cellular senescence by targeting mafa |
| topic | stearic acid melatonin micrornas cellular senescence mafa |
| url | http://www.e-enm.org/upload/pdf/enm-2022-1565.pdf |
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