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Renal scattered tubular-like cells confer protective effects in the stenotic murine kidney mediated by release of extracellular vesicles.

Renal scattered tubular-like cells confer protective effects in the stenotic murine kidney mediated by release of extracellular vesicles.
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Zou X, Kwon SH, Jiang K, Ferguson CM, Puranik AS, Zhu X, Lerman LO,


Zou X, Kwon SH, Jiang K, Ferguson CM, Puranik AS, Zhu X, Lerman LO, (click to view)

Zou X, Kwon SH, Jiang K, Ferguson CM, Puranik AS, Zhu X, Lerman LO,

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Scientific reports 2018 01 198(1) 1263 doi 10.1038/s41598-018-19750-y
Abstract

To test the hypothesis that intrinsic renal scattered tubular cells (STC-like cells) contribute to repairing injured tubular epithelial cells (TEC) by releasing extracellular vesicle (EV). EV released from primary cultured pig STC-like cells were confirmed by electron microscopy. Antimycin-A (AMA)-induced injured proximal TEC (PK1 cells) were co-cultured with STC-like cells, STC-like cells-derived EV, or EV-free conditioned-medium for 3 days. Cellular injury, oxidative stress and mitochondrial function were assessed. Transfer of mitochondria from STC-like cells to TEC was assessed using Mito-trackers, and their viability by mitochondrial membrane potential assays. STC-like cells-derived EV were intra-arterially injected into mice 2 weeks after induction of unilateral renal artery stenosis. Two weeks later, renal hemodynamics were studied using magnetic-resonance-imaging, and renal fibrosis assessed ex-vivo. Cultured STC-like cells released EV that were uptaken by TEC. A protective effect conferred by STC-like cells in AMA-induced TEC injury was partly mimicked by their EV. Furthermore, STC-like cells-EV carried and transferred mitochondrial material to injured TEC, which partly restored mitochondrial function. In vivo, STC-like cells-derived EV engrafted in the stenotic kidney, and improved its perfusion and oxygenation. STC-like cells-EV exert protective effects on injured tubular cells in vitro and in vivo, partly by transferring STC-like cells mitochondria, which remain at least partly functional in recipient TEC.

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