Lopes 2022 Int J Mol Sci

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Lopes JA, Collino F, Rodrigues-Ferreira C, Sampaio LDS, Costa-Sarmento G, Wendt CHC, Almeida FP, Miranda KR, Kasai-Brunswick TH, Lindoso RS, Vieyra A (2022) Early effects of extracellular vesicles secreted by adipose tissue mesenchymal cells in renal ischemia followed by reperfusion: mechanisms rely on a decrease in mitochondrial anion superoxide production. https://doi.org/10.3390/ijms23062906

Β» Int J Mol Sci 23:2906. PMID: 35328327 Open Access

Lopes Jarlene A,  Collino Federica,  Rodrigues-Ferreira Clara,  da Silva Sampaio Luzia,  Costa-Sarmento Gloria,  Wendt Camila HC, Almeida Fernando P,  Miranda Kildare R,  Kasai-Brunswick Tais H,  Lindoso Rafael S,  Vieyra Adalberto (2022) Int J Mol Sci

Abstract: Acute kidney injury (AKI) caused by ischemia followed by reperfusion (I/R) is characterized by intense anion superoxide (O2β€’-) production and oxidative damage. We investigated whether extracellular vesicles secreted by adipose tissue mesenchymal cells (EVs) administered during reperfusion can suppress the exacerbated mitochondrial O2β€’- formation after I/R. We used Wistar rats subjected to bilateral renal arterial clamping (30 min) followed by 24 h of reperfusion. The animals received EVs (I/R + EVs group) or saline (I/R group) in the kidney subcapsular space. The third group consisted of false-operated rats (SHAM). Mitochondria were isolated from proximal tubule cells and used immediately. Amplex Redβ„’ was used to measure mitochondrial O2β€’- formation and MitoTrackerβ„’ Orange to evaluate inner mitochondrial membrane potential (Ξ”Οˆ). In vitro studies were carried out on human renal proximal tubular cells (HK-2) co-cultured or not with EVs under hypoxic conditions. Administration of EVs restored O2β€’- formation to SHAM levels in all mitochondrial functional conditions. The gene expression of catalase and superoxide dismutase-1 remained unmodified; transcription of heme oxygenase-1 (HO-1) was upregulated. The co-cultures of HK-2 cells with EVs revealed an intense decrease in apoptosis. We conclude that the mechanisms by which EVs favor long-term recovery of renal structures and functions after I/R rely on a decrease of mitochondrial O2β€’- formation with the aid of the upregulated antioxidant HO-1/Nuclear factor erythroid 2-related factor 2 system, thus opening new vistas for the treatment of AKI. β€’ Keywords: Acellular therapy, Anion superoxide, Extracellular vesicles, Mesenchymal cells, Mitochondria, Proximal tubular cells, Regenerative medicine, Renal ischemia/reperfusion β€’ Bioblast editor: Plangger M


Labels: MiParea: Respiration 

Stress:Ischemia-reperfusion  Organism: Human  Tissue;cell: Kidney  Preparation: Isolated mitochondria 


Coupling state: LEAK, OXPHOS, ET  Pathway: S, ROX  HRR: Oxygraph-2k, O2k-Fluorometer 

2022-12, AmR 

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