MondoA and AKI and AKI-to-CKD Transition

Maeda, Shihomi; Sakai, Shinsuke; Takabatake, Yoshitsugu; Yamamoto, Takeshi; Minami, Satoshi; Nakamura, Jun; Namba-Hamano, Tomoko; Takahashi, Atsushi; Matsuda, Jun; Yonishi, Hiroaki; Matsui, Sho; Imai, Atsuhiro; Edahiro, Ryuya; Yamamoto-Imoto, Hitomi; Matsui, Isao; Takashima, Seiji; Imamura, Ryoichi; Nonomura, Norio; Yanagita, Motoko; Okada, Yukinori; Ballabio, Andrea; Nakamura, Shuhei; Yoshimori, Tamotsu; Isaka, Yoshitaka

doi:https://doi.org/10.1681/ASN.0000000000000414

MondoA and AKI and AKI-to-CKD Transition

Maeda, Shihomi; Sakai, Shinsuke; Takabatake, Yoshitsugu et al.

Journal of the American Society of Nephrology, 2024, 35(9), 1164-1182

Number of Access:4,860（2025-10-31 04:28 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/97232

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Title	MondoA and AKI and AKI-to-CKD Transition
Creator	CreatorName Maeda, Shihomi
	NRID 1000060817360 1000060817360 CreatorName Sakai, Shinsuke
	NRID 1000030403075 1000030403075 CreatorName Takabatake, Yoshitsugu
	NRID 1000020756994 1000020756994 researchmap permalink tyamamoto-handai3857 tyamamoto-handai3857 Scopus Author ID 55628566248 55628566248 ORCID 0009-0007-3817-0557 0009-0007-3817-0557 CreatorName Yamamoto, Takeshi
	NRID 1000000791592 1000000791592 researchmap permalink minami415 minami415 Scopus Author ID 57188809277 57188809277 ORCID 0000-0001-5043-3435 0000-0001-5043-3435 CreatorName Minami, Satoshi
	NRID 1000010846679 1000010846679 CreatorName Nakamura, Jun
	NRID 1000030734420 1000030734420 researchmap permalink namba-handai3857 namba-handai3857 Scopus Author ID 8577526800 8577526800 ORCID 0000-0002-6049-7616 0000-0002-6049-7616 CreatorName Namba-Hamano, Tomoko
	NRID 1000010704786 1000010704786 researchmap permalink takahashi-handai3857 takahashi-handai3857 Scopus Author ID 55728349700 55728349700 CreatorName Takahashi, Atsushi
	NRID 1000010778260 1000010778260 researchmap permalink jun_matsuda jun_matsuda ORCID 0000-0003-1492-6157 0000-0003-1492-6157 CreatorName Matsuda, Jun
	NRID 1000040822143 1000040822143 CreatorName Yonishi, Hiroaki
	NRID 1000070974286 1000070974286 CreatorName Matsui, Sho
	CreatorName Imai, Atsuhiro
	researchmap permalink ryuya_edahiro_88 ryuya_edahiro_88 NRID 1000010998008 1000010998008 ORCID 0000-0001-5009-6408 0000-0001-5009-6408 Scopus Author ID 56227394200 56227394200 CreatorName Edahiro, Ryuya
	NRID 1000050532230 1000050532230 researchmap permalink hitomiimoto hitomiimoto Scopus Author ID 57204087325 57204087325 CreatorName Yamamoto-Imoto, Hitomi
	NRID 1000060456986 1000060456986 ORCID 0000-0001-8378-6130 0000-0001-8378-6130 researchmap permalink matsui-handai3857 matsui-handai3857 Scopus Author ID 24488796300 24488796300 CreatorName Matsui, Isao
	NRID 1000090379272 1000090379272 researchmap permalink read0118567 read0118567 Scopus Author ID 7402272558 7402272558 CreatorName Takashima, Seiji
	NRID 1000040456976 1000040456976 CreatorName Imamura, Ryoichi
	NRID 1000030263263 1000030263263 researchmap permalink read0185096 read0185096 Scopus Author ID 7005880662 7005880662 CreatorName Nonomura, Norio
	NRID 1000070378769 1000070378769 CreatorName Yanagita, Motoko
	NRID 1000070727411 1000070727411 ORCID 0000-0002-0311-8472 0000-0002-0311-8472 researchmap permalink yokada yokada Scopus Author ID 35976475900 35976475900 CreatorName Okada, Yukinori
	CreatorName Ballabio, Andrea
	NRID 1000000510611 1000000510611 ORCID 0000-0002-1488-8317 0000-0002-1488-8317 researchmap permalink shuhei shuhei Scopus Author ID 55468273400 55468273400 CreatorName Nakamura, Shuhei
	NRID 1000060191649 1000060191649 researchmap permalink read0085516 read0085516 Scopus Author ID 7006810223 7006810223 CreatorName Yoshimori, Tamotsu
	NRID 1000000379166 1000000379166 researchmap permalink isaka-handai3857 isaka-handai3857 Scopus Author ID 16207611100 16207611100 ORCID 0000-0002-0820-7167 0000-0002-0820-7167 CreatorName Isaka, Yoshitaka
Subject	AKI
	CKD
	fibrosis
	hypoxia
	ischemia-reperfusion
	kidney biopsy
	kidney tubule
	mitochondria
	molecular biology
	transcription factors
Description	Maeda S., Sakai S., Takabatake Y., et al. MondoA and AKI and AKI-to-CKD Transition. Journal of the American Society of Nephrology , (2024); https://doi.org/10.1681/ASN.0000000000000414.
Abstract	Key PointsThe expression of MondoA was decreased in the renal tubules of patients with CKD.Genetic ablation of MondoA in proximal tubules inhibited autophagy and increased vulnerability to AKI through increased expression of Rubicon.MondoA ablation during the recovery phase after ischemia-reperfusion aggravated kidney injury through downregulation of the transcription factor EB-peroxisome proliferator-activated receptor-γ coactivator-1α axis.BackgroundElderly individuals and patients with CKD are at a higher risk of AKI. The transcription factor MondoA is downregulated in the kidneys of aged individuals or patients with AKI; however, its roles in AKI development and the AKI-to-CKD transition remain unknown.MethodsWe investigated the expression of MondoA in human kidney biopsy samples, ischemia-reperfusion-injured (IRI) mouse kidneys, and cultured proximal tubular epithelial cells under hypoxia/reoxygenation. The role of MondoA during the initial and recovery phases after IRI was evaluated using proximal tubule-specific MondoA knockout mice and MondoA-deficient proximal tubular epithelial cells. Furthermore, we explored the involvement of Rubicon and transcription factor EB (TFEB), both of which are downstream factors of MondoA.ResultsMONDOA expression was decreased in the renal tubules of patients with CKD. In mouse kidneys, MondoA expression was decreased under ischemia, whereas its expression was increased during reperfusion. Genetic ablation of MondoA in proximal tubular epithelial cells inhibited autophagy and increased vulnerability to AKI through increased expression of Rubicon. Ablation of Rubicon in MondoA-deficient IRI kidneys activated autophagy and protected mitochondrial function. MondoA ablation during the recovery phase after ischemia-reperfusion aggravated kidney injury through downregulation of the TFEB-peroxisome proliferator-activated receptor-γ coactivator-1α axis. Pharmacological upregulation of TFEB contributed to maintaining mitochondrial biogenesis and increased peroxisome proliferator-activated receptor-γ coactivator-1α transcription.ConclusionsOur findings demonstrate that MondoA protected against vulnerability to AKI by maintaining autophagy and subsequently supporting mitochondrial function to prevent progression to CKD.
Publisher	Wolters Kluwer Health
Source Title	Journal of the American Society of Nephrology
Volume (Issue)	35(9)
Page	1164-1182
Date of Issued	2024-05-31
Language	English
Handle URL	https://hdl.handle.net/11094/97232
PISSN	10466673
eISSN	15333450
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1681/ASN.0000000000000414
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Journal of the American Society of Nephrology. 2024, 35(9), p. 1164-1182
DC.title	MondoA and AKI and AKI-to-CKD Transition
DC.creator	Maeda, Shihomi
	Sakai, Shinsuke
	Takabatake, Yoshitsugu
	Yamamoto, Takeshi
	Minami, Satoshi
	Nakamura, Jun
	Namba-Hamano, Tomoko
	Takahashi, Atsushi
	Matsuda, Jun
	Yonishi, Hiroaki
	Matsui, Sho
	Imai, Atsuhiro
	Edahiro, Ryuya
	Yamamoto-Imoto, Hitomi
	Matsui, Isao
	Takashima, Seiji
	Imamura, Ryoichi
	Nonomura, Norio
	Yanagita, Motoko
	Okada, Yukinori
	Ballabio, Andrea
	Nakamura, Shuhei
	Yoshimori, Tamotsu
	Isaka, Yoshitaka
DC.publisher	Wolters Kluwer Health
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-05-31
DC.identifier	https://doi.org/10.1681/ASN.0000000000000414
DC.subject	AKI
	CKD
	fibrosis
	hypoxia
	ischemia-reperfusion
	kidney biopsy
	kidney tubule
	mitochondria
	molecular biology
	transcription factors
DC.description	Maeda S., Sakai S., Takabatake Y., et al. MondoA and AKI and AKI-to-CKD Transition. Journal of the American Society of Nephrology , (2024); https://doi.org/10.1681/ASN.0000000000000414.
DCTERMS.abstract	Key PointsThe expression of MondoA was decreased in the renal tubules of patients with CKD.Genetic ablation of MondoA in proximal tubules inhibited autophagy and increased vulnerability to AKI through increased expression of Rubicon.MondoA ablation during the recovery phase after ischemia-reperfusion aggravated kidney injury through downregulation of the transcription factor EB-peroxisome proliferator-activated receptor-γ coactivator-1α axis.BackgroundElderly individuals and patients with CKD are at a higher risk of AKI. The transcription factor MondoA is downregulated in the kidneys of aged individuals or patients with AKI; however, its roles in AKI development and the AKI-to-CKD transition remain unknown.MethodsWe investigated the expression of MondoA in human kidney biopsy samples, ischemia-reperfusion-injured (IRI) mouse kidneys, and cultured proximal tubular epithelial cells under hypoxia/reoxygenation. The role of MondoA during the initial and recovery phases after IRI was evaluated using proximal tubule-specific MondoA knockout mice and MondoA-deficient proximal tubular epithelial cells. Furthermore, we explored the involvement of Rubicon and transcription factor EB (TFEB), both of which are downstream factors of MondoA.ResultsMONDOA expression was decreased in the renal tubules of patients with CKD. In mouse kidneys, MondoA expression was decreased under ischemia, whereas its expression was increased during reperfusion. Genetic ablation of MondoA in proximal tubular epithelial cells inhibited autophagy and increased vulnerability to AKI through increased expression of Rubicon. Ablation of Rubicon in MondoA-deficient IRI kidneys activated autophagy and protected mitochondrial function. MondoA ablation during the recovery phase after ischemia-reperfusion aggravated kidney injury through downregulation of the TFEB-peroxisome proliferator-activated receptor-γ coactivator-1α axis. Pharmacological upregulation of TFEB contributed to maintaining mitochondrial biogenesis and increased peroxisome proliferator-activated receptor-γ coactivator-1α transcription.ConclusionsOur findings demonstrate that MondoA protected against vulnerability to AKI by maintaining autophagy and subsequently supporting mitochondrial function to prevent progression to CKD.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	97232
citation_title	MondoA and AKI and AKI-to-CKD Transition
citation_author	Maeda, Shihomi
	Sakai, Shinsuke
	Takabatake, Yoshitsugu
	Yamamoto, Takeshi
	Minami, Satoshi
	Nakamura, Jun
	Namba-Hamano, Tomoko
	Takahashi, Atsushi
	Matsuda, Jun
	Yonishi, Hiroaki
	Matsui, Sho
	Imai, Atsuhiro
	Edahiro, Ryuya
	Yamamoto-Imoto, Hitomi
	Matsui, Isao
	Takashima, Seiji
	Imamura, Ryoichi
	Nonomura, Norio
	Yanagita, Motoko
	Okada, Yukinori
	Ballabio, Andrea
	Nakamura, Shuhei
	Yoshimori, Tamotsu
	Isaka, Yoshitaka
citation_publisher	Wolters Kluwer Health
citation_language	English
citation_date	2024-05-31
citation_journal_title	Journal of the American Society of Nephrology
citation_volume	35
citation_issue	9
citation_firstpage	1164
citation_lastpage	1182
citation_doi	https://doi.org/10.1681/ASN.0000000000000414
citation_public_url	https://hdl.handle.net/11094/97232

MondoA and AKI and AKI-to-CKD Transition

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