miR-125b Disrupts Mitochondrial Dynamics via Targeting Mitofusin 1 in Cisplatin-Induced Acute Kidney Injury

Background: Mitochondria are dynamic organelles whose structure are maintained by continuous fusion and fission. During acute kidney injury (AKI) progression, mitochondrial fission in renal tubular cells was elevated, characterized by mitochondrial fragmentation. It is tightly associated with mitoch...

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Autores principales:	Yue Zhao, Yue Lang, Mingchao Zhang, Shaoshan Liang, Xiaodong Zhu, Zhihong Liu
Formato:	article
Lenguaje:	EN
Publicado:	Karger Publishers 2021
Materias:	mir-125b acute kidney injury cisplatin mitochondrial fragmentation Internal medicine RC31-1245
Acceso en línea:	https://doaj.org/article/c8956efae8bd47b38fa60b6b5e14180c
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spelling	oai:doaj.org-article:c8956efae8bd47b38fa60b6b5e14180c2021-12-02T12:40:23ZmiR-125b Disrupts Mitochondrial Dynamics via Targeting Mitofusin 1 in Cisplatin-Induced Acute Kidney Injury2296-93812296-935710.1159/000520140https://doaj.org/article/c8956efae8bd47b38fa60b6b5e14180c2021-11-01T00:00:00Zhttps://www.karger.com/Article/FullText/520140https://doaj.org/toc/2296-9381https://doaj.org/toc/2296-9357Background: Mitochondria are dynamic organelles whose structure are maintained by continuous fusion and fission. During acute kidney injury (AKI) progression, mitochondrial fission in renal tubular cells was elevated, characterized by mitochondrial fragmentation. It is tightly associated with mitochondrial dysfunction, which has been proven as a critical mechanism responsible for AKI. However, the initiating factor for the disruption of mitochondrial dynamics in AKI was not well understood. Objectives: To explore the molecular mechanisms of mitochondrial disorders and kidney damage. Methods: We established cisplatin-induced AKI model in C57BL/6 mice and proximal tubular cells, and detected the expression of miR-125b by qPCR. Then we delivered miR-125b antagomir after cisplatin treatment in mice via hydrodynamic-based gene transfer technique. Subsequently, we performed luciferase reporter and immunoblotting assays to prove miR-125b could directly modulate mitofusin1 (MFN1) expression. We also tested the role of miR-125b in mitochondrial and renal injury through immunofluorescent staining, qPCR, and immunoblotting assays. Results: miR-125b levels were induced in cisplatin-challenged mice and cultured tubular cells. Anti-miR-125b could effectively alleviate cisplatin-induced mitochondrial fragmentation and kidney injury both in vitro and in vivo. Furthermore, miR-125b could directly regulate MFN1, which is a key regulator of mitochondrial fusion. Our study indicated that miR-125b is upregulated during cisplatin-induced AKI. Inhibition of miR-125b may suppress mitochondrial and renal damage through upregulating MFN1. This study suggests that miR-125b could be a potential therapeutic target in AKI.Yue ZhaoYue LangMingchao ZhangShaoshan LiangXiaodong ZhuZhihong LiuKarger Publishersarticlemir-125bacute kidney injurycisplatinmitochondrial fragmentationInternal medicineRC31-1245ENKidney Diseases, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mir-125b acute kidney injury cisplatin mitochondrial fragmentation Internal medicine RC31-1245
spellingShingle	mir-125b acute kidney injury cisplatin mitochondrial fragmentation Internal medicine RC31-1245 Yue Zhao Yue Lang Mingchao Zhang Shaoshan Liang Xiaodong Zhu Zhihong Liu miR-125b Disrupts Mitochondrial Dynamics via Targeting Mitofusin 1 in Cisplatin-Induced Acute Kidney Injury
description	Background: Mitochondria are dynamic organelles whose structure are maintained by continuous fusion and fission. During acute kidney injury (AKI) progression, mitochondrial fission in renal tubular cells was elevated, characterized by mitochondrial fragmentation. It is tightly associated with mitochondrial dysfunction, which has been proven as a critical mechanism responsible for AKI. However, the initiating factor for the disruption of mitochondrial dynamics in AKI was not well understood. Objectives: To explore the molecular mechanisms of mitochondrial disorders and kidney damage. Methods: We established cisplatin-induced AKI model in C57BL/6 mice and proximal tubular cells, and detected the expression of miR-125b by qPCR. Then we delivered miR-125b antagomir after cisplatin treatment in mice via hydrodynamic-based gene transfer technique. Subsequently, we performed luciferase reporter and immunoblotting assays to prove miR-125b could directly modulate mitofusin1 (MFN1) expression. We also tested the role of miR-125b in mitochondrial and renal injury through immunofluorescent staining, qPCR, and immunoblotting assays. Results: miR-125b levels were induced in cisplatin-challenged mice and cultured tubular cells. Anti-miR-125b could effectively alleviate cisplatin-induced mitochondrial fragmentation and kidney injury both in vitro and in vivo. Furthermore, miR-125b could directly regulate MFN1, which is a key regulator of mitochondrial fusion. Our study indicated that miR-125b is upregulated during cisplatin-induced AKI. Inhibition of miR-125b may suppress mitochondrial and renal damage through upregulating MFN1. This study suggests that miR-125b could be a potential therapeutic target in AKI.
format	article
author	Yue Zhao Yue Lang Mingchao Zhang Shaoshan Liang Xiaodong Zhu Zhihong Liu
author_facet	Yue Zhao Yue Lang Mingchao Zhang Shaoshan Liang Xiaodong Zhu Zhihong Liu
author_sort	Yue Zhao
title	miR-125b Disrupts Mitochondrial Dynamics via Targeting Mitofusin 1 in Cisplatin-Induced Acute Kidney Injury
title_short	miR-125b Disrupts Mitochondrial Dynamics via Targeting Mitofusin 1 in Cisplatin-Induced Acute Kidney Injury
title_full	miR-125b Disrupts Mitochondrial Dynamics via Targeting Mitofusin 1 in Cisplatin-Induced Acute Kidney Injury
title_fullStr	miR-125b Disrupts Mitochondrial Dynamics via Targeting Mitofusin 1 in Cisplatin-Induced Acute Kidney Injury
title_full_unstemmed	miR-125b Disrupts Mitochondrial Dynamics via Targeting Mitofusin 1 in Cisplatin-Induced Acute Kidney Injury
title_sort	mir-125b disrupts mitochondrial dynamics via targeting mitofusin 1 in cisplatin-induced acute kidney injury
publisher	Karger Publishers
publishDate	2021
url	https://doaj.org/article/c8956efae8bd47b38fa60b6b5e14180c
work_keys_str_mv	AT yuezhao mir125bdisruptsmitochondrialdynamicsviatargetingmitofusin1incisplatininducedacutekidneyinjury AT yuelang mir125bdisruptsmitochondrialdynamicsviatargetingmitofusin1incisplatininducedacutekidneyinjury AT mingchaozhang mir125bdisruptsmitochondrialdynamicsviatargetingmitofusin1incisplatininducedacutekidneyinjury AT shaoshanliang mir125bdisruptsmitochondrialdynamicsviatargetingmitofusin1incisplatininducedacutekidneyinjury AT xiaodongzhu mir125bdisruptsmitochondrialdynamicsviatargetingmitofusin1incisplatininducedacutekidneyinjury AT zhihongliu mir125bdisruptsmitochondrialdynamicsviatargetingmitofusin1incisplatininducedacutekidneyinjury
_version_	1718393766657654784

miR-125b Disrupts Mitochondrial Dynamics via Targeting Mitofusin 1 in Cisplatin-Induced Acute Kidney Injury

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