PMID- 35880571 OWN - NLM STAT- MEDLINE DCOM- 20220727 LR - 20230211 IS - 1745-7270 (Electronic) IS - 1672-9145 (Print) IS - 1672-9145 (Linking) VI - 54 IP - 7 DP - 2022 Jun 25 TI - Circular RNA-VPS13A attenuates diabetes-induced enteric glia damage by targeting miR-182/GDNF Axis. PG - 999-1007 LID - 10.3724/abbs.2022073 [doi] AB - 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. FAU - Zhu, Xiaowei AU - Zhu X AD - Department of Endocrinology and Metabolism, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. AD - Department of Endocrinology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214000, China. FAU - Li, Yanyu AU - Li Y AD - Department of Endocrinology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214000, China. FAU - Zhu, Xuping AU - Zhu X AD - Department of Endocrinology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214000, China. FAU - Wang, Ke AU - Wang K AD - NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China. FAU - Zhu, Xue AU - Zhu X AD - NHC Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China. FAU - Jiang, Yanmin AU - Jiang Y AD - Department of Endocrinology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214000, China. FAU - Xu, Lan AU - Xu L AD - Department of Endocrinology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 214000, China. FAU - Li, Jianbo AU - Li J AD - Department of Endocrinology and Metabolism, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China. LA - eng PT - Journal Article PL - China TA - Acta Biochim Biophys Sin (Shanghai) JT - Acta biochimica et biophysica Sinica JID - 101206716 RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) SB - IM MH - Animals MH - *Diabetes Mellitus, Experimental/complications/genetics/metabolism MH - Glial Cell Line-Derived Neurotrophic Factor/genetics MH - *Hyperglycemia/genetics/metabolism MH - In Situ Hybridization, Fluorescence MH - Mice MH - *MicroRNAs/metabolism MH - Neuroglia MH - Quality of Life MH - RNA, Circular/genetics PMC - PMC9828216 OTO - NOTNLM OT - circVPS13A OT - diabetes mellitus OT - enteric glia OT - gastrointestinal complications COIS- The authors declare that they have no conflict of interest. EDAT- 2022/07/27 06:00 MHDA- 2022/07/28 06:00 PMCR- 2022/07/08 CRDT- 2022/07/26 05:32 PHST- 2022/07/26 05:32 [entrez] PHST- 2022/07/27 06:00 [pubmed] PHST- 2022/07/28 06:00 [medline] PHST- 2022/07/08 00:00 [pmc-release] AID - 10.3724/abbs.2022073 [doi] PST - ppublish SO - Acta Biochim Biophys Sin (Shanghai). 2022 Jun 25;54(7):999-1007. doi: 10.3724/abbs.2022073.