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Updated: Jun 25, 2025
Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
Published on: January 7, 2013
Autophagy-deficient macrophages exacerbate cisplatin-induced mitochondrial dysfunction and kidney injury via
Yujia Yuan1, Longhui Yuan1, Jingchao Yang1
1National Health Commission (NHC) Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, China.
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.
Insights
Macrophages autophagy influences kidney injury. Impaired macrophage autophagy, via exosomal miR-195a-5p, damages tubular cells and worsens acute kidney injury (AKI). Activating autophagy may protect kidneys.
Area of Science:
- Cell Biology
- Renal Physiology
- Immunology
Background:
- Macrophage (Mφ) autophagy is crucial in inflammatory diseases.
- The specific role of Mφ autophagy in acute kidney injury (AKI) pathogenesis remains unclear.
Purpose of the Study:
- To elucidate the mechanistic role of Mφ autophagy in AKI progression.
- To investigate the crosstalk between Mφ and tubular epithelial cells (TECs) in AKI.
Main Methods:
- Utilized cisplatin-induced AKI mouse models with Mφ-specific ATG7 depletion (Atg7Δmye).
- Analyzed Mφ-derived exosomes and their impact on TECs in vitro and in vivo.
- Investigated the role of miR-195a-5p and SIRT3 in the Mφ-TEC communication axis.
- Administered trehalose to modulate Mφ autophagy in AKI models.
Main Results:
- Mφ autophagy was activated then inhibited in cisplatin-induced AKI.
- Mφ-specific ATG7 deletion aggravated kidney injury and tubulointerstitial inflammation.
- Exosomes from Atg7Δmye Mφ impaired TEC mitochondrial function via miR-195a-5p enrichment and SIRT3 interaction.
- miR-195a-5p inhibition or SIRT3 overexpression improved mitochondrial bioenergetics and renal function.
- Trehalose treatment alleviated AKI when Mφ autophagy was activated.
Conclusions:
- Exosomal miR-195a-5p mediates communication between autophagy-deficient Mφ and TECs in AKI.
- The miR-195a-5p-SIRT3 axis impairs TEC mitochondrial biogenesis, exacerbating kidney injury.
- Modulating Mφ autophagy presents a potential therapeutic strategy for AKI.
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