Transfer of microRNA-486-5p from human endothelial colony forming cell–derived exosomes reduces ischemic kidney injury

Administration of human cord blood endothelial colony-forming cells (ECFCs) or their exosomes protects mice against kidney ischemia/reperfusion injury. Here we studied the microRNA (miRNA) content of ECFC exosomes and the role of miRNA transfer in kidney and endothelial cell protection. ECFC exosomes were enriched in miR-486-5p, which targets the phosphatase and tensin homolog (PTEN) and the Akt pathway. In cultured endothelial cells exposed to hypoxia, incubation with ECFC exosomes increased miR-486-5p, decreased PTEN, and stimulated Akt phosphorylation. Exposure of hypoxic endothelial cells to conditioned medium from ECFCs pretreated with anti–miR-486-5p blocked increases in miR-486-5p and phosphorylated Akt, restored expression of PTEN, and enhanced apoptosis. Coculture of endothelial cells with ECFCs enhanced endothelial miR-486-5p levels. Targeting of PTEN by miR-486-5p was observed in endothelial cells, and PTEN knockdown blocked apoptosis. In mice with ischemic kidney injury, infusion of ECFC exosomes induced potent functional and histologic protection, associated with increased kidney miR-486-5p levels, decreased PTEN, and activation of Akt. Infusion of exosomes from ECFCs transfected with anti–miR-486-5p had no protective effect. Thus, delivery of ECFC exosomes reduces ischemic kidney injury via transfer of miR-486-5p targeting PTEN. Exosomes enriched in miR-486-5p could represent a therapeutic tool in acute kidney injury. Administration of human cord blood endothelial colony-forming cells (ECFCs) or their exosomes protects mice against kidney ischemia/reperfusion injury. Here we studied the microRNA (miRNA) content of ECFC exosomes and the role of miRNA transfer in kidney and endothelial cell protection. ECFC exosomes were enriched in miR-486-5p, which targets the phosphatase and tensin homolog (PTEN) and the Akt pathway. In cultured endothelial cells exposed to hypoxia, incubation with ECFC exosomes increased miR-486-5p, decreased PTEN, and stimulated Akt phosphorylation. Exposure of hypoxic endothelial cells to conditioned medium from ECFCs pretreated with anti–miR-486-5p blocked increases in miR-486-5p and phosphorylated Akt, restored expression of PTEN, and enhanced apoptosis. Coculture of endothelial cells with ECFCs enhanced endothelial miR-486-5p levels. Targeting of PTEN by miR-486-5p was observed in endothelial cells, and PTEN knockdown blocked apoptosis. In mice with ischemic kidney injury, infusion of ECFC exosomes induced potent functional and histologic protection, associated with increased kidney miR-486-5p levels, decreased PTEN, and activation of Akt. Infusion of exosomes from ECFCs transfected with anti–miR-486-5p had no protective effect. Thus, delivery of ECFC exosomes reduces ischemic kidney injury via transfer of miR-486-5p targeting PTEN. Exosomes enriched in miR-486-5p could represent a therapeutic tool in acute kidney injury. Ischemia/reperfusion (IR) is a major cause of acute kidney injury (AKI) in humans, and is associated with tubular cell necrosis and endothelial cell dysfunction and loss.1Basile D.P. The endothelial cell in ischemic acute kidney injury: implications for acute and chronic function.Kidney Int. 2007; 72: 151-156Abstract Full Text Full Text PDF PubMed Scopus (349) Google Scholar, 2Basile D.P. Anderson M.D. Sutton T.A. Pathophysiology of acute kidney injury.Compr Physiol. 2012; 2: 1303-1353Crossref PubMed Scopus (665) Google Scholar, 3Bonventre J.V. Yang L. Cellular pathophysiology of ischemic acute kidney injury.J Clin Invest. 2011; 121: 4210-4221Crossref PubMed Scopus (1326) Google Scholar No treatments have been shown to accelerate kidney repair in humans. In experimental AKI administration of certain stem or progenitor cells improves kidney histologic and functional recovery with no requirement for cell engraftment, indicating that repair pathways may be activated by paracrine factors released by the cells.4Morigi M. Benigni A. Mesenchymal stem cells and kidney repair.Nephrol Dial Transplant. 2013; 28: 788-793Crossref PubMed Scopus (83) Google Scholar, 5Patschan D. Patschan S. Muller G.A. Endothelial progenitor cells in acute ischemic kidney injury: strategies for increasing the cells' renoprotective competence.Int J Nephrol. 2011; 2011 ([e-pub ahead of 2011 Apr 27]) (Accessed May 6, 2015): 828369http://dx.doi.org/10.4061/2011/828369Crossref PubMed Google Scholar, 6Togel F.E. Westenfelder C. 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Tada T. et al.Endothelial dysfunction in ischemic acute renal failure: rescue by transplanted endothelial cells.Am J Physiol Renal Physiol. 2002; 282: F1140-F1149Crossref PubMed Scopus (258) Google Scholar In this regard, endothelial colony-forming cells (ECFCs) are early lineage endothelial progenitors that can be isolated from human cord blood or peripheral blood.8Yoder M.C. Mead L.E. Prater D. et al.Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals.Blood. 2007; 109: 1801-1809Crossref PubMed Scopus (1241) Google Scholar We recently demonstrated that administration of human cord blood ECFCs to nonobese diabetic severe combined immunodeficient (NOD-SCID) mice with IR AKI exerted protective effects, with diminished levels of tubular necrosis, apoptosis, oxidative stress, and inflammatory cell infiltrate.9Burger D. Viñas J.L. Akbari S. et al.Human endothelial colony forming cells protect against acute kidney injury: role of exosomes.Am J Pathol. 2015; 185: 2309-2323Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar Notably, delivery of small extracellular vesicles (exosomes) derived from ECFCs to mice also protected against kidney injury and inhibited apoptosis in cultured endothelial cells exposed to hypoxia/reoxygenation (HR).9Burger D. Viñas J.L. Akbari S. et al.Human endothelial colony forming cells protect against acute kidney injury: role of exosomes.Am J Pathol. 2015; 185: 2309-2323Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar These findings are consistent with the beneficial effects of stem cell– or progenitor cell–derived vesicles on kidney recovery in other rodent models of AKI.10Bruno S. Grange C. Deregibus M.C. et al.Mesenchymal stem cell-derived microvesicles protect against acute tubular injury.J Am Soc Nephrol. 2009; 20: 1053-1067Crossref PubMed Scopus (999) Google Scholar, 11Bruno S. Grange C. Collino F. et al.Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury.PLoS One. 2012; 7: e33115Crossref PubMed Scopus (478) Google Scholar, 12Cantaluppi V. Gatti S. Medica D. et al.Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia-reperfusion injury by microRNA-dependent reprogramming of resident renal cells.Kidney Int. 2012; 82: 412-427Abstract Full Text Full Text PDF PubMed Scopus (416) Google Scholar, 13Sanchez M.B. Bruno S. Grange C. et al.Human liver stem cells and derived extracellular vesicles improve recovery in a murine model of acute kidney injury.Stem Cell Res Ther. 2014; 5: 124Crossref PubMed Scopus (78) Google Scholar MicroRNAs (miRNAs) are 18- to 25-nucleotide RNA species that have profound effects on protein translation via binding to complementary regions of mRNA, usually in the 3′ untranslated region (UTR).14Mendell J.T. Olson E.N. MicroRNAs in stress signaling and human disease.Cell. 2012; 148: 1172-1187Abstract Full Text Full Text PDF PubMed Scopus (1304) Google Scholar Extracellular vesicles selectively package miRNA species, and the transfer of miRNAs from cell-derived vesicles to recipient cells can regulate protein expression and contribute to reparative signaling responses.15Das S. Halushka M.K. Extracellular vesicle microRNA transfer in cardiovascular disease.Cardiovasc Pathol. 2015; 24: 199-206Abstract Full Text Full Text PDF PubMed Scopus (128) Google Scholar In experimental AKI, depletion of proangiogenic miR-126 and miR-296 from extracellular vesicles derived from human endothelial progenitor cells inhibited their kidney reparative effects in vivo and reduced their antiapoptotic effects in cultured cells.12Cantaluppi V. Gatti S. Medica D. et al.Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia-reperfusion injury by microRNA-dependent reprogramming of resident renal cells.Kidney Int. 2012; 82: 412-427Abstract Full Text Full Text PDF PubMed Scopus (416) Google Scholar In mice with glycerol-induced AKI, global depletion of miRNAs from mesenchymal stromal cell–derived extracellular vesicles by Drosha knockdown blocked their beneficial effects on kidney functional and morphologic recovery.16Collino F. Pomatto M. Camussi G. et al.AKI recovery induced by mesenchymal stromal cell-derived extracellular vesicles carrying microRNAs.J Am Soc Nephrol. 2015; 26: 2349-2360Crossref PubMed Scopus (183) Google Scholar Thus, miRNA transfer from extracellular vesicles may be involved in accelerating repair after AKI. In the current studies, we determined the role of exosomal miRNA transfer in the protective effects on IR injury. Using Next Generation Sequencing, we defined the differential miRNA expression pattern in 2 classes of ECFC-derived extracellular vesicles: exosomes (40- to 100-nm diameter) and microparticles (MPs, 100- to 1000-nm diameter). Our results indicate an abundance of miR-486-5p within ECFC exosomes and suggest a role in recovery from IR injury in vivo and protection against endothelial cell apoptosis in vitro via miRNA transfer and targeting of phosphatase and tensin homolog (PTEN), with activation of Akt. We first characterized small RNA libraries from ECFCs and their exosomes and MPs. Exosomes had a mean diameter of 91 nm and expressed the surface marker TSG101, whereas MPs had a mean diameter of 224 nm and lacked TSG101 (Figure 1). After eliminating transfer RNA, 158 miRNAs were isolated by Next Generation the of miRNAs was to vesicles and a was to or ECFCs and miRNAs were to on from 2 of miRNA In ECFC miR-486-5p was levels in MPs ECFC (Figure The expressed miRNAs were levels in MPs. The differential levels of miR-486-5p exosomes and MPs were also by (Figure on the role of exosomal miR-486-5p in ischemic colony-forming cell exosomes are enriched in the (miRNAs) in ECFC exosomes with microparticles miR-486-5p levels in ECFC exosomes and by In cultured human endothelial cells exposed to administration of ECFC-derived conditioned medium or exosomes increased miR-486-5p levels, whereas conditioned medium from ECFCs transfected with to miR-486-5p blocked this (Figure PTEN, a of miR-486-5p, is involved in signaling through the Akt V. et of signaling by A. PubMed Scopus Google Scholar, et of signaling pathways improves Clin Invest. 2014; PubMed Scopus Google Scholar increased PTEN an blocked by ECFC-derived exosomes (Figure of Akt was in exposed to administration of ECFC-derived exosomes stimulated Akt (Figure We that ECFC-derived exosomes activation induced by in D. Viñas J.L. Akbari S. et al.Human endothelial colony forming cells protect against acute kidney injury: role of exosomes.Am J Pathol. 2015; 185: 2309-2323Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar the role of miR-486-5p transfer from ECFC exosomes in endothelial protection, were to and exposed to conditioned medium from ECFCs that had been transfected with or to shown in PTEN expression was blocked by ECFC-derived conditioned conditioned medium from ECFCs transfected with to miR-486-5p to increases in PTEN. ECFC-derived conditioned medium increased Akt in to whereas conditioned medium from ECFCs transfected with to miR-486-5p blocked this (Figure induced a significant in in and ECFC-derived conditioned medium inhibited this (Figure the other conditioned medium from ECFCs transfected with to miR-486-5p The transfer of miR-486-5p was studied in of ECFCs and exposed to the of et and transfer of in PubMed Scopus Google Scholar, M. M.C. et the inflammatory to 2015; Scopus Google Scholar or the of pathways and in PubMed Scopus Google Scholar, S. V. L. et of miR-126 in endothelial cells and of chronic 2014; PubMed Scopus Google Scholar, T. et through and and 2014; PubMed Scopus Google Scholar increases in levels of miR-486-5p were observed in with cultured (Figure of cells with or blocked this of ECFCs with to with increases in miR-486-5p levels which were inhibited by or of ECFC-derived exosomes was studied the In with exosomes with were within by (Figure of with exosomes in the of inhibited whereas had no on of exosomal miR-486-5p targets PTEN in a was a a complementary miR-486-5p in (Figure transfected with the were with ECFC exosomes or with miR-486-5p was reduced (Figure The of exosomes on was blocked were first transfected with to In exosomes of with a miR-486-5p reduced cells were transfected with a of the PTEN (Figure the role of PTEN in endothelial cell apoptosis, were in in which PTEN expression was decreased by small RNA to and with ECFC of with to PTEN reduced PTEN protein expression and activation in to in with knockdown of PTEN, exosomes had no on activation in to (Figure In of with or incubation with the had no on activation in to The of exosomal miR-486-5p transfer in protection from kidney IR injury in vivo was studied in were to kidney IR and with or ECFC exosomes by infusion of mice exosomes derived from ECFCs that were first transfected with to miR-486-5p, which in significant depletion of exosomal miR-486-5p levels Kidney levels of miR-486-5p in mice to after this administration a significant (Figure with exosomes derived from ECFCs transfected with a in kidney miR-486-5p levels. Kidney PTEN expression was increased after and administration inhibited was observed in mice with exosomes from ECFCs transfected with Kidney Akt was increased in mice with in mice that exosomes from We that administration of ECFCs or their exosomes to mice with kidney IR injury has renal functional and histologic protective D. Viñas J.L. Akbari S. et al.Human endothelial colony forming cells protect against acute kidney injury: role of exosomes.Am J Pathol. 2015; 185: 2309-2323Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar we levels of miR-486-5p, PTEN, and phosphorylated Akt in from Kidney miR-486-5p levels increased after IR in and with ECFCs or exosomes after IR induced significant increases with exosomes inhibited kidney PTEN expression and stimulated Akt in mice with IR shown in administration of exosomes to mice with IR potent protection against kidney injury after as by of and blood decreased of and diminished histologic injury. of apoptosis and activation were also reduced by (Figure These protective effects were in mice that exosomes derived from ECFCs that were transfected with to effects of endothelial colony-forming cell exosomes on apoptosis in mice with kidney ischemia/reperfusion (IR) injury: role of of in from mice mice with kidney mice with kidney IR with ECFC exosomes the of and mice with kidney IR with exosomes derived from ECFCs transfected with to miR-486-5p after are as of kidney from indicate of apoptosis had kidney in the of mice after of extracellular vesicles derived from endothelial progenitor cells protects against experimental kidney IR injury, and transfer of miRNA to recipient cells has been in the reparative D. Viñas J.L. Akbari S. et al.Human endothelial colony forming cells protect against acute kidney injury: role of exosomes.Am J Pathol. 2015; 185: 2309-2323Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar, 12Cantaluppi V. Gatti S. Medica D. et al.Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia-reperfusion injury by microRNA-dependent reprogramming of resident renal cells.Kidney Int. 2012; 82: 412-427Abstract Full Text Full Text PDF PubMed Scopus (416) Google Scholar, F. Pomatto M. Camussi G. et al.AKI recovery induced by mesenchymal stromal cell-derived extracellular vesicles carrying microRNAs.J Am Soc Nephrol. 2015; 26: 2349-2360Crossref PubMed Scopus (183) Google Scholar The current indicate that transfer of miR-486-5p from ECFC-derived exosomes to endothelial cells an role in apoptosis after kidney is by ECFC-derived exosomes are enriched in miR-486-5p, and delivery of exosomes to 2 with kidney IR injury or to cultured endothelial cells exposed to hypoxic injury increases miR-486-5p levels, PTEN and Akt ECFC-derived conditioned medium in cultured endothelial cells associated with of PTEN expression and Akt effects that are blocked by miR-486-5p transfer of miR-486-5p from ECFCs to endothelial cells in and is blocked by of exosomal and miR-486-5p targets PTEN in cultured endothelial cells, and knockdown of PTEN expression and ECFC exosomes protect against kidney IR injury in an that is ECFCs are first transfected with to miRNA have been in kidney IR injury proangiogenic miR-126 and V. Gatti S. Medica D. et al.Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia-reperfusion injury by microRNA-dependent reprogramming of resident renal cells.Kidney Int. 2012; 82: 412-427Abstract Full Text Full Text PDF PubMed Scopus (416) Google Scholar T. C. et renal injury.J Am Soc Nephrol. 2015; Scopus Google Scholar and et of a microRNA of renal A. PubMed Scopus Google Scholar We miR-296 or in and miR-126 and were in ECFC-derived levels were increased with ECFCs or MPs. an we demonstrated that ECFC exosomes are enriched in miR-486-5p with ECFCs or MPs. other expressed or in could a role in the protective effects on IR injury, miR-486-5p is a for antiapoptotic effects in vivo and in Thus, miR-486-5p has been shown to PTEN in in the antiapoptotic et of signaling pathways improves Clin Invest. 2014; PubMed Scopus Google Scholar is to AKI enhanced Akt is associated with kidney in mice with IR D. et renal ischemia-reperfusion injury by targeting Am Soc Nephrol. 2014; PubMed Scopus Google Scholar Our indicate targeting of endothelial cell PTEN by exosomal miR-486-5p, that this to enhanced Akt and of apoptosis. Thus, delivery of exosomes to mice with kidney IR injury was associated with reduced kidney expression of PTEN and enhanced Akt by increased levels of In cultured exposed to ECFC exosomes or conditioned increased miR-486-5p levels, and the effects of ECFC conditioned on PTEN, Akt, and were by of ECFCs with miR-486-5p of PTEN in was associated with decreased the of Akt activation by exosomes in to PTEN was defined in Thus, Akt to be a to PTEN V. et of signaling by A. PubMed Scopus Google Scholar, et of signaling pathways improves Clin Invest. 2014; PubMed Scopus Google Scholar the 2 signaling targets in apoptosis after kidney IR suggest that reduced PTEN expression may be protective after the of PTEN In a model of kidney et et a of and signaling renal J Physiol Renal Physiol. 2012; PubMed Scopus Google Scholar that of PTEN in to and a which may contribute to chronic kidney after AKI. and of delivery of exosomes enriched in miR-486-5p after AKI be to In in vivo studies, mice had increased kidney PTEN expression after a for increased miR-486-5p levels, with In mice with kidney we also observed increased PTEN with enhanced kidney miR-486-5p levels. Thus, miR-486-5p levels may have to a PTEN expression in the kidney after in to PTEN, other targets of miR-486-5p be in the protective targets for miR-486-5p the which has been in signaling and in chronic kidney L. et the of in chronic kidney is inhibited by Int. 2012; 82: Full Text Full Text PDF PubMed Scopus Google Scholar and which is associated with of and experimental et effects and of in 2015; 5: PubMed Scopus Google Scholar In miR-486-5p targets leading to of activation and of cell et which is in by targeting 2015; 282: PubMed Scopus Google Scholar Our on endothelial cells as major targets of exosomal transfer of miR-486-5p after ischemic injury. the renal may be the for exosomes after in vivo In a model of kidney IR injury, et V. Gatti S. Medica D. et al.Microvesicles derived from endothelial progenitor cells protect the kidney from ischemia-reperfusion injury by microRNA-dependent reprogramming of resident renal cells.Kidney Int. 2012; 82: 412-427Abstract Full Text Full Text PDF PubMed Scopus (416) Google Scholar microvesicles from endothelial progenitor cells to and tubular cells, that renal or cells could also be of exosomal transfer after In in studies, levels of miR-486-5p in cultured endothelial cells were enhanced after hypoxia, whereas kidney levels of miR-486-5p increased in mice and to in mice after These suggest that kidney cells other the may be induced to miR-486-5p in the reparative In the current studies, miR-486-5p levels increased cells were with ECFCs and ECFCs were first transfected with a for of cells with which by et and transfer of in PubMed Scopus Google Scholar, M. M.C. et the inflammatory to 2015; Scopus Google Scholar miR-486-5p levels. The of this on was by an of the and pathways and in PubMed Scopus Google Scholar, S. V. L. et of miR-126 in endothelial cells and of chronic 2014; PubMed Scopus Google Scholar, T. et through and and 2014; PubMed Scopus Google Scholar decreased miR-486-5p levels in cells and blocked miRNAs have been to in with which their of et a of of vesicles in human A. 2011; PubMed Scopus Google Scholar indicate that miR-486-5p is selectively enriched within ECFC which transfer this miRNA to endothelial In human cord blood ECFCs exosomes enriched in In vitro exosomal transfer of miR-486-5p to endothelial cells, with targeting of the pathway. of exosomes to mice with kidney IR injury potent protective effects associated with decreased kidney PTEN and activation of Akt. These effects are observed with exosomes of The results suggest that the of human exosomes may be a to protect against endothelial injury in AKI. libraries were from RNA from and the RNA libraries were from ECFC-derived exosomes and MPs and with a of ECFC small targeting miRNAs and other small were to of the RNA and an was to were of were by the to miRNA of to was the and of were with the The from were to human miRNAs in with were and no were in the kidney IR was on to mice as in on D. Viñas J.L. Akbari S. et al.Human endothelial colony forming cells protect against acute kidney injury: role of exosomes.Am J Pathol. 2015; 185: 2309-2323Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar after of blood mice ECFC exosomes or exosomes derived from ECFCs that were first transfected with to miR-486-5p microRNA were by and mice were after mice were to renal vascular were by the the of and to the of the for and blood levels were by were in in and as D. Viñas J.L. Akbari S. et al.Human endothelial colony forming cells protect against acute kidney injury: role of exosomes.Am J Pathol. 2015; 185: 2309-2323Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar injury was in a by a renal with on a of to D. Viñas J.L. Akbari S. et al.Human endothelial colony forming cells protect against acute kidney injury: role of exosomes.Am J Pathol. 2015; 185: 2309-2323Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar was on kidney by of in a was the were on a with a ECFCs were cultured from human cord blood The and following and with from the and characterized as D. Viñas J.L. Akbari S. et al.Human endothelial colony forming cells protect against acute kidney injury: role of exosomes.Am J Pathol. 2015; 185: 2309-2323Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar, et and of endothelial colony forming cells is enhanced by One. 2013; PubMed Scopus Google Scholar were from the and cultured as D. Viñas J.L. Akbari S. et al.Human endothelial colony forming cells protect against acute kidney injury: role of exosomes.Am J Pathol. 2015; 185: 2309-2323Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar of ECFCs and ECFCs were and with or or transfected with or After the were to with and for cells were with or or In ECFCs were transfected with to miR-486-5p, of exosomes from the cell PTEN expression was decreased by of cells with Exosomes and MPs were isolated from medium by as D. Viñas J.L. Akbari S. et al.Human endothelial colony forming cells protect against acute kidney injury: role of exosomes.Am J Pathol. 2015; 185: 2309-2323Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar after of in the of of extracellular vesicles was by analysis with a as D. Viñas J.L. Akbari S. et al.Human endothelial colony forming cells protect against acute kidney injury: role of exosomes.Am J Pathol. 2015; 185: 2309-2323Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar, D. et microparticles diabetic injury.J Am Soc Nephrol. 2014; PubMed Scopus Google Scholar, C. et vesicle and by (Accessed 2015): Scholar RNA of the small RNA was the The was for were in an RNA was to in RNA levels of The of miRNA to RNA was expressed the 2 model for in PubMed Scopus Google Scholar were hypoxic for cells were this with conditioned medium from conditioned medium from ECFCs transfected with or medium ECFC-derived exosomes S. et of endothelial progenitor cell-derived microvesicles on endothelial dysfunction and Cell 2013; PubMed Scopus Google Scholar After of hypoxia, were for an Kidney and were on and with against Akt Cell phosphorylated Akt Cell PTEN Cell or for were with to TSG101 were with and by were and for was the D. Viñas J.L. Akbari S. et al.Human endothelial colony forming cells protect against acute kidney injury: role of exosomes.Am J Pathol. 2015; 185: 2309-2323Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar Exosomes were with the S. et of by 2012; PubMed Scopus Google Scholar for After exosomes were in and with for were with was an and with were as a with The or PTEN were transfected with or with to miR-486-5p After was a were on an are expressed as mean and were or analysis of with as were with was the no These were by from the of The of and the Kidney of is by a The C. of for with the hypoxia/reoxygenation and C. and G. for with the of phosphatase and tensin homolog (PTEN) expression by RNA in cultured human endothelial cells is for PTEN, with is from 2 is from exposed to and are from of transfected with RNA against PTEN. is from transfected with miR-486-5p levels in exosomes derived from endothelial colony-forming cells (ECFCs) transfected with to results of for miR-486-5p in exosomes from ECFCs and from ECFCs transfected with miR-486-5p for and their exosomes kidney miR-486-5p levels, phosphatase and tensin homolog (PTEN), and enhance Akt after ischemia/reperfusion (IR) in severe combined immunodeficient for miR-486-5p on kidney RNA, after IR and endothelial colony-forming cell of ECFC on kidney miR-486-5p levels after of ECFC on kidney PTEN expression after IR ECFC or of ECFC exosomes on kidney PTEN expression after IR or of ECFC on kidney phosphorylated Akt after of ECFC exosomes on kidney after to kidney for in for PTEN and are shown for and and for and Akt for and and for miR-486-5p and miR-486-5p are shown with within the 3′ untranslated region of phosphatase and tensin homolog (PTEN) was the The binding for miR-486-5p is was to the MicroRNAs in extracellular vesicles protect kidney from ischemic injury: from endothelial to tubular vesicles from stem cells or progenitor cells are therapeutic for acute kidney injury. exosomes of extracellular Viñas et ischemic the by exosomes to the injury by targeting phosphatase and tensin homolog and endothelial cell apoptosis. In this we the and the of their on extracellular vesicle PDF exosomes for the of acute kidney are as a delivery for the of acute kidney injury. In this of Kidney et a to the exosomal of mice and after renal that exosomes renal signaling and acute kidney injury. for significant and in acute kidney injury. PDF

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