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circMTND5 Participates in Renal Mitochondrial Injury and Fibrosis by Sponging MIR6812 in Lupus Nephritis

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...

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Autores principales: Luan, Junjun, Jiao, Congcong, Ma, Cong, Zhang, Yixiao, Hao, Xiangnan, Zhou, Guangyu, Fu, Jingqi, Qiu, Xingyu, Li, Hongyu, Yang, Wei, Illei, Gabor G., Kopp, Jeffrey B., Pi, Jingbo, Zhou, Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9578797/
https://www.ncbi.nlm.nih.gov/pubmed/36267809
http://dx.doi.org/10.1155/2022/2769487
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author Luan, Junjun
Jiao, Congcong
Ma, Cong
Zhang, Yixiao
Hao, Xiangnan
Zhou, Guangyu
Fu, Jingqi
Qiu, Xingyu
Li, Hongyu
Yang, Wei
Illei, Gabor G.
Kopp, Jeffrey B.
Pi, Jingbo
Zhou, Hua
author_facet Luan, Junjun
Jiao, Congcong
Ma, Cong
Zhang, Yixiao
Hao, Xiangnan
Zhou, Guangyu
Fu, Jingqi
Qiu, Xingyu
Li, Hongyu
Yang, Wei
Illei, Gabor G.
Kopp, Jeffrey B.
Pi, Jingbo
Zhou, Hua
author_sort Luan, Junjun
collection PubMed
description 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-β 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.
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spelling pubmed-95787972022-10-19 circMTND5 Participates in Renal Mitochondrial Injury and Fibrosis by Sponging MIR6812 in Lupus Nephritis Luan, Junjun Jiao, Congcong Ma, Cong Zhang, Yixiao Hao, Xiangnan Zhou, Guangyu Fu, Jingqi Qiu, Xingyu Li, Hongyu Yang, Wei Illei, Gabor G. Kopp, Jeffrey B. Pi, Jingbo Zhou, Hua Oxid Med Cell Longev Research Article 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-β 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. Hindawi 2022-10-11 /pmc/articles/PMC9578797/ /pubmed/36267809 http://dx.doi.org/10.1155/2022/2769487 Text en Copyright © 2022 Junjun Luan et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Luan, Junjun
Jiao, Congcong
Ma, Cong
Zhang, Yixiao
Hao, Xiangnan
Zhou, Guangyu
Fu, Jingqi
Qiu, Xingyu
Li, Hongyu
Yang, Wei
Illei, Gabor G.
Kopp, Jeffrey B.
Pi, Jingbo
Zhou, Hua
circMTND5 Participates in Renal Mitochondrial Injury and Fibrosis by Sponging MIR6812 in Lupus Nephritis
title circMTND5 Participates in Renal Mitochondrial Injury and Fibrosis by Sponging MIR6812 in Lupus Nephritis
title_full circMTND5 Participates in Renal Mitochondrial Injury and Fibrosis by Sponging MIR6812 in Lupus Nephritis
title_fullStr circMTND5 Participates in Renal Mitochondrial Injury and Fibrosis by Sponging MIR6812 in Lupus Nephritis
title_full_unstemmed circMTND5 Participates in Renal Mitochondrial Injury and Fibrosis by Sponging MIR6812 in Lupus Nephritis
title_short circMTND5 Participates in Renal Mitochondrial Injury and Fibrosis by Sponging MIR6812 in Lupus Nephritis
title_sort circmtnd5 participates in renal mitochondrial injury and fibrosis by sponging mir6812 in lupus nephritis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9578797/
https://www.ncbi.nlm.nih.gov/pubmed/36267809
http://dx.doi.org/10.1155/2022/2769487
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