Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Early Effects of Extracellular Vesicles Secreted by Adipose Tissue Mesenchymal Cells in Renal Ischemia Followed by Reperfusion: Mechanisms Rely on the Restoration of the Redox Tissular Environment

Version 1 : Received: 1 February 2022 / Approved: 3 February 2022 / Online: 3 February 2022 (10:07:54 CET)

A peer-reviewed article of this Preprint also exists.

Lopes, J.A.; Collino, F.; Rodrigues-Ferreira, C.; Sampaio, L.S.; Costa-Sarmento, G.; Wendt, C.H.C.; Almeida, F.P.; Miranda, K.R.; Kasai-Brunswick, T.H.; Lindoso, R.S.; Vieyra, A. 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. Int. J. Mol. Sci. 2022, 23, 2906. Lopes, J.A.; Collino, F.; Rodrigues-Ferreira, C.; Sampaio, L.S.; Costa-Sarmento, G.; Wendt, C.H.C.; Almeida, F.P.; Miranda, K.R.; Kasai-Brunswick, T.H.; Lindoso, R.S.; Vieyra, A. 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. Int. J. Mol. Sci. 2022, 23, 2906.

Abstract

Acute kidney injury (AKI) caused by ischemia followed by reperfusion (I/R) is characterized by intense anion superoxide (O2•-) production and oxidative damage. We investigated whether extracellular vesicles secreted by adipose tissue mesenchymal cells (EVs) administrated during reperfusion can suppress the exacerbated mitochondrial O2•- formation after I/R. We used Wistar rats submitted 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 3rd group was of the false-operated rats (SHAM). Mitochondria were isolated from proximal tubule cells and immediately used. Amplex Red™ was used to measure mitochondrial O2•- formation and MitoTracker® Orange to evaluate Δψ. In vitro studies were carried out by using human renal proximal tubular cells (HK-2) co-cultured or not with EVs under hypoxia conditions. Administration of EVs restored O2•- formation to SHAM levels in all mitochondrial functional conditions. The expression of catalase and superoxide dismutase 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 recover the renal structure and function after I/R are related to the normalization of the mitochondrial redox environment. The intravesicular catalase is central in the preservation mechanisms that, with the aid of the upregulated antioxidant HO-1/Nuclear factor erythroid 2-related factor 2 system, depress early processes of cell death after I/R and open new vistas for the treatment of AKI.

Keywords

extracellular vesicles; mesenchymal cells; proximal tubular cells; renal ischemia/reperfusion; mitochondria; anion superoxide; acellular therapy; regenerative medicine

Subject

Biology and Life Sciences, Biochemistry and Molecular Biology

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