| First Author | Yuan Y | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 4383 |
| PubMed ID | 38782909 | Mgi Jnum | J:350366 |
| Mgi Id | MGI:7644735 | Doi | 10.1038/s41467-024-47842-z |
| Citation | Yuan Y, et al. (2024) Autophagy-deficient macrophages exacerbate cisplatin-induced mitochondrial dysfunction and kidney injury via miR-195a-5p-SIRT3 axis. Nat Commun 15(1):4383 |
| abstractText | Macrophages (Mphi) 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 Mphi promote AKI progression via crosstalk with tubular epithelial cells (TECs), and autophagy of Mphi was activated and then inhibited in cisplatin-induced AKI mice. Mphi-specific depletion of ATG7 (Atg7(Deltamye)) aggravated kidney injury in AKI mice, which was associated with tubulointerstitial inflammation. Moreover, Mphi-derived exosomes from Atg7(Deltamye) 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 Mphi from AKI mice to Mphi-depleted mice promotes the kidney injury response to cisplatin, which is alleviated when Mphi autophagy is activated with trehalose. We conclude that exosomal miR-195a-5p mediate the communication between autophagy-deficient Mphi and TECs, leading to impaired mitochondrial biogenetic in TECs and subsequent exacerbation of kidney injury in AKI mice via miR-195a-5p-SIRT3 axis. |
