Circular RNA-VPS13A attenuates diabetes-induced enteric glia damage by targeting miR-182/GDNF axis
Gastrointestinal (GI) complications of diabetes mellitus (DM) significantly impact on patients’ quality of life. Enteric glial cells (EGC) are the key cell type of enteric nervous system (ENS), which contributes to the destruction of gut homeostasis in DM. Circular RNAs (circRNAs) are a novel type o...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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China Science Publishing & Media Ltd.
2022-07-01
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| Series: | Acta Biochimica et Biophysica Sinica |
| Subjects: | |
| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2022073 |
| _version_ | 1797635324275326976 |
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| author | Zhu Xiaowei Li Yanyu Zhu Xuping Wang Ke Zhu Xue Jiang Yanmin Xu Lan Li Jianbo |
| author_facet | Zhu Xiaowei Li Yanyu Zhu Xuping Wang Ke Zhu Xue Jiang Yanmin Xu Lan Li Jianbo |
| author_sort | Zhu Xiaowei |
| collection | DOAJ |
| description | Gastrointestinal (GI) complications of diabetes mellitus (DM) significantly impact on patients’ quality of life. Enteric glial cells (EGC) are the key cell type of enteric nervous system (ENS), which contributes to the destruction of gut homeostasis in DM. Circular RNAs (circRNAs) are a novel type of RNAs abundant in the eukaryotic transcriptome, which form covalently closed continuous loops. In this study, the contribution of circRNAs to EGC damage in DM is investigated. Transcriptome sequencing analysis and functional study show that circVPS13A is significantly down-regulated in hyperglycemia-treated EGC, and circVPS13A overexpression attenuates EGC damage in both in vitro and in vivo DM models. In vitro mechanistic study using dual-luciferase reporter assay, affinity-isolation assay, fluorescence in situ hybridization (FISH) and immunostaining analysis identify that circVPS13A exerts its protective effect by sponging miR-182 and then up-regulates glial cell line-derived neurotrophic factor (GDNF) expression. In addition, in vivo study confirms that the circVPS13A-miR-182-GDNF network regulation can attenuate hyperglycemia-induced EGC damage of duodenum in streptozotocine (STZ)-induced DM mice. The findings of this study may provide novel insights into the protective role of circVPS13A in DM-associated EGC damage and clues for the development of new therapeutic approaches for the prevention of GI complications of DM. |
| first_indexed | 2024-03-11T12:20:37Z |
| format | Article |
| id | doaj.art-3bd46c0984ad4207b66b91b129927379 |
| institution | Directory Open Access Journal |
| issn | 1672-9145 |
| language | English |
| last_indexed | 2024-03-11T12:20:37Z |
| publishDate | 2022-07-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj.art-3bd46c0984ad4207b66b91b1299273792023-11-07T01:00:39ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452022-07-0154999100710.3724/abbs.202207320d259ccCircular RNA-VPS13A attenuates diabetes-induced enteric glia damage by targeting miR-182/GDNF axisZhu Xiaowei0Li Yanyu1Zhu Xuping2Wang Ke3Zhu Xue4Jiang Yanmin5Xu Lan6Li Jianbo7["Department of Endocrinology and Metabolism, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China","Department of Endocrinology, Wuxi People′s Hospital Affiliated to Nanjing Medical University, Wuxi 214000, China"]["Department of Endocrinology, Wuxi People′s Hospital Affiliated to Nanjing Medical University, Wuxi 214000, China"]["Department of Endocrinology, Wuxi People′s Hospital Affiliated to Nanjing Medical University, Wuxi 214000, China"]["NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China"]["NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China"]["Department of Endocrinology, Wuxi People′s Hospital Affiliated to Nanjing Medical University, Wuxi 214000, China"]["Department of Endocrinology, Wuxi People′s Hospital Affiliated to Nanjing Medical University, Wuxi 214000, China"]["Department of Endocrinology and Metabolism, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China"]Gastrointestinal (GI) complications of diabetes mellitus (DM) significantly impact on patients’ quality of life. Enteric glial cells (EGC) are the key cell type of enteric nervous system (ENS), which contributes to the destruction of gut homeostasis in DM. Circular RNAs (circRNAs) are a novel type of RNAs abundant in the eukaryotic transcriptome, which form covalently closed continuous loops. In this study, the contribution of circRNAs to EGC damage in DM is investigated. Transcriptome sequencing analysis and functional study show that circVPS13A is significantly down-regulated in hyperglycemia-treated EGC, and circVPS13A overexpression attenuates EGC damage in both in vitro and in vivo DM models. In vitro mechanistic study using dual-luciferase reporter assay, affinity-isolation assay, fluorescence in situ hybridization (FISH) and immunostaining analysis identify that circVPS13A exerts its protective effect by sponging miR-182 and then up-regulates glial cell line-derived neurotrophic factor (GDNF) expression. In addition, in vivo study confirms that the circVPS13A-miR-182-GDNF network regulation can attenuate hyperglycemia-induced EGC damage of duodenum in streptozotocine (STZ)-induced DM mice. The findings of this study may provide novel insights into the protective role of circVPS13A in DM-associated EGC damage and clues for the development of new therapeutic approaches for the prevention of GI complications of DM.https://www.sciengine.com/doi/10.3724/abbs.2022073diabetes mellitusgastrointestinal complicationsenteric gliacircVPS13A |
| spellingShingle | Zhu Xiaowei Li Yanyu Zhu Xuping Wang Ke Zhu Xue Jiang Yanmin Xu Lan Li Jianbo Circular RNA-VPS13A attenuates diabetes-induced enteric glia damage by targeting miR-182/GDNF axis Acta Biochimica et Biophysica Sinica diabetes mellitus gastrointestinal complications enteric glia circVPS13A |
| title | Circular RNA-VPS13A attenuates diabetes-induced enteric glia damage by targeting miR-182/GDNF axis |
| title_full | Circular RNA-VPS13A attenuates diabetes-induced enteric glia damage by targeting miR-182/GDNF axis |
| title_fullStr | Circular RNA-VPS13A attenuates diabetes-induced enteric glia damage by targeting miR-182/GDNF axis |
| title_full_unstemmed | Circular RNA-VPS13A attenuates diabetes-induced enteric glia damage by targeting miR-182/GDNF axis |
| title_short | Circular RNA-VPS13A attenuates diabetes-induced enteric glia damage by targeting miR-182/GDNF axis |
| title_sort | circular rna vps13a attenuates diabetes induced enteric glia damage by targeting mir 182 gdnf axis |
| topic | diabetes mellitus gastrointestinal complications enteric glia circVPS13A |
| url | https://www.sciengine.com/doi/10.3724/abbs.2022073 |
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