PMID- 36267809 OWN - NLM STAT- MEDLINE DCOM- 20221025 LR - 20221025 IS - 1942-0994 (Electronic) IS - 1942-0900 (Print) IS - 1942-0994 (Linking) VI - 2022 DP - 2022 TI - circMTND5 Participates in Renal Mitochondrial Injury and Fibrosis by Sponging MIR6812 in Lupus Nephritis. PG - 2769487 LID - 10.1155/2022/2769487 [doi] LID - 2769487 AB - Recent studies have focused on nuclear-encoded circular RNAs (circRNAs) in kidney diseases, but little is known about mitochondrial circRNAs. Differentially expressed circRNAs were analyzed by RNA deep sequencing from lupus nephritis (LN) biopsies and normal human kidneys. In LN renal biopsies, the most downregulated circRNA was circMTND5, which is encoded in the mitochondrial genome. We quantitated circMTND5 by qPCR and localized by fluorescence in situ hybridization (FISH). Mitochondrial abnormalities were identified by electron microscopy. The expression of mitochondrial genes was decreased, and the expression of profibrotic genes was increased on qPCR and immunostaining. RNA binding sites for MIR6812 and circMTND5 were predicted. MIR6812 expression was increased by FISH and qPCR. In HK-2 cells and its mitochondrial fraction, the role of circMTND5 sponging MIR6812 was assessed by their colocalization in mitochondria on FISH, RNA immunoprecipitation, and RNA pulldown coupled with luciferase reporter assay. circMTND5 knockdown upregulated MIR6812, decreased mitochondrial functional gene expression, and increased profibrotic gene expression. Overexpression of circMTND5 reversed these effects in hTGF-beta stimulated HK-2 cells. Similar effects were observed in HK-2 cells with overexpression and with knockdown of MIR6812. We conclude that circMTND5 alleviates renal mitochondrial injury and kidney fibrosis by sponging MIR6812 in LN. CI - Copyright (c) 2022 Junjun Luan et al. FAU - Luan, Junjun AU - Luan J AD - Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China. FAU - Jiao, Congcong AU - Jiao C AD - Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China. FAU - Ma, Cong AU - Ma C AD - Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China. FAU - Zhang, Yixiao AU - Zhang Y AD - Department of Urology, Shengjing Hospital of China Medical University, Shenyang, China. FAU - Hao, Xiangnan AU - Hao X AD - Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China. FAU - Zhou, Guangyu AU - Zhou G AD - Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China. FAU - Fu, Jingqi AU - Fu J AD - Program of Environmental Toxicology, School of Public Health, China Medical University, Shenyang, China. FAU - Qiu, Xingyu AU - Qiu X AD - Department of Physiology, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, China. FAU - Li, Hongyu AU - Li H AD - Shensu Science & Technology Co. Ltd., Suzhou, China. FAU - Yang, Wei AU - Yang W AD - Shensu Science & Technology Co. Ltd., Suzhou, China. FAU - Illei, Gabor G AU - Illei GG AD - Horizon, Gaithersburg, MD, USA. FAU - Kopp, Jeffrey B AU - Kopp JB AD - Kidney Disease Section, NIDDK, NIH, Bethesda, USA. FAU - Pi, Jingbo AU - Pi J AD - Program of Environmental Toxicology, School of Public Health, China Medical University, Shenyang, China. FAU - Zhou, Hua AU - Zhou H AUID- ORCID: 0000-0003-0429-116X AD - Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China. LA - eng PT - Journal Article DEP - 20221011 PL - United States TA - Oxid Med Cell Longev JT - Oxidative medicine and cellular longevity JID - 101479826 RN - 0 (MicroRNAs) RN - 0 (RNA, Circular) RN - EC 1.6.99.3 (MT-ND5 protein, human) SB - IM MH - Humans MH - Fibrosis MH - In Situ Hybridization, Fluorescence MH - Kidney/pathology MH - *Kidney Diseases/genetics/metabolism MH - *Lupus Nephritis/genetics/metabolism/pathology MH - *MicroRNAs/genetics/metabolism MH - Mitochondria/metabolism MH - *RNA, Circular/genetics PMC - PMC9578797 COIS- The authors have no relevant financial or nonfinancial interests to disclose. EDAT- 2022/10/22 06:00 MHDA- 2022/10/25 06:00 PMCR- 2022/10/11 CRDT- 2022/10/21 03:01 PHST- 2022/05/17 00:00 [received] PHST- 2022/09/12 00:00 [revised] PHST- 2022/09/22 00:00 [accepted] PHST- 2022/10/21 03:01 [entrez] PHST- 2022/10/22 06:00 [pubmed] PHST- 2022/10/25 06:00 [medline] PHST- 2022/10/11 00:00 [pmc-release] AID - 10.1155/2022/2769487 [doi] PST - epublish SO - Oxid Med Cell Longev. 2022 Oct 11;2022:2769487. doi: 10.1155/2022/2769487. eCollection 2022.