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Autophagy-deficient macrophages exacerbate cisplatin-induced mitochondrial dysfunction and kidney injury via miR-195a-5p-SIRT3 axis

Authors :
Yujia Yuan
Longhui Yuan
Jingchao Yang
Fei Liu
Shuyun Liu
Lan Li
Guangneng Liao
Xi Tang
Jingqiu Cheng
Jingping Liu
Younan Chen
Yanrong Lu
Source :
Nature Communications, Vol 15, Iss 1, Pp 1-17 (2024)
Publication Year :
2024
Publisher :
Nature Portfolio, 2024.

Abstract

Abstract Macrophages (Mφ) autophagy is a pivotal contributor to inflammation-related diseases. However, the mechanistic details of its direct role in acute kidney injury (AKI) were unclear. Here, we show that Mφ promote AKI progression via crosstalk with tubular epithelial cells (TECs), and autophagy of Mφ was activated and then inhibited in cisplatin-induced AKI mice. Mφ-specific depletion of ATG7 (Atg7Δmye) aggravated kidney injury in AKI mice, which was associated with tubulointerstitial inflammation. Moreover, Mφ-derived exosomes from Atg7Δmye mice impaired TEC mitochondria in vitro, which may be attributable to miR-195a-5p enrichment in exosomes and its interaction with SIRT3 in TECs. Consistently, either miR-195a-5p inhibition or SIRT3 overexpression improved mitochondrial bioenergetics and renal function in vivo. Finally, adoptive transfer of Mφ from AKI mice to Mφ-depleted mice promotes the kidney injury response to cisplatin, which is alleviated when Mφ autophagy is activated with trehalose. We conclude that exosomal miR-195a-5p mediate the communication between autophagy-deficient Mφ and TECs, leading to impaired mitochondrial biogenetic in TECs and subsequent exacerbation of kidney injury in AKI mice via miR-195a-5p-SIRT3 axis.

Subjects

Subjects :
Science

Details

Language :
English
ISSN :
20411723
Volume :
15
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
edsdoj.58c616ab08413db1b6d2eddbc13b21
Document Type :
article
Full Text :
https://doi.org/10.1038/s41467-024-47842-z