Transcriptomics

Dataset Information

96

Role of miRNAs in acute kidney injury recovery induced by mesenchymal stromal cells and derived extracellular vesicles.


ABSTRACT: Phenotypic changes induced by extracellular vesicles (EVs) have been implicated in the recovery of acute kidney injury (AKI) induced by mesenchymal stromal cells (MSCs). miRNAs are potential candidates for cell reprogramming towards a pro-regenerative phenotype. The aim of the present study was to evaluate whether miRNA de-regulation inhibits the regenerative potential of MSCs and derived-EVs in a model of glycerol-induced AKI in SCID mice. For this purpose, we generated MSCs depleted of Drosha, a critical enzyme of miRNA maturation, to alter miRNA expression within MSCs and EVs. Drosha knock-down MSCs (MSC-Dsh) maintained the phenotype and differentiation capacity. They produced EVs that did not differ from those of wild type cells in quantity, surface molecule expression and internalization within renal tubular epithelial cells. However, EVs derived from MSC-Dsh (EV-Dsh) showed global down-regulation of miRNAs. Whereas, wild type MSCs and derived EVs were able to induce morphological and functional recovery in AKI, MSC-Dsh and EV-Dsh were ineffective. RNA sequencing analysis showed that genes deregulated in the kidney of AKI mice were restored by treatment with MSCs and EVs but not by MSC-Dsh and EV-Dsh. Gene Ontology analysis showed that down-regulated genes in AKI were associated with fatty acid metabolism. The up-regulated genes in AKI were involved in inflammation, ECM-receptor interaction and cell adhesion molecules. These alterations were reverted by treatment with wild type MSCs and EVs, but not by the Drosha counterparts. In conclusion, miRNA depletion in MSCs and EVs significantly reduced their intrinsic regenerative potential in AKI, suggesting a critical role of miRNAs. RNA-seq

ORGANISM(S): Mus musculus  

SUBMITTER: Francesco Neri  Salvatore Oliviero   Federica Collino   Daniela Dettori   Peter Quesenberry   Ciro Tetta   Danny Incarnato   Giovanni Camussi   Stefania Bruno    

PROVIDER: E-GEOD-59958 | ArrayExpress| 2015-05-22

SECONDARY ACCESSION(S): GSE59958SRP045150PRJNA257193

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs.

Collino Federica F   Bruno Stefania S   Incarnato Danny D   Dettori Daniela D   Neri Francesco F   Provero Paolo P   Pomatto Margherita M   Oliviero Salvatore S   Tetta Ciro C   Quesenberry Peter J PJ   Camussi Giovanni G  

Journal of the American Society of Nephrology : JASN 20150421 10


Phenotypic changes induced by extracellular vesicles have been implicated in mesenchymal stromal cell-promoted recovery of AKI. MicroRNAs are potential candidates for cell reprogramming toward a proregenerative phenotype. The aim of this study was to evaluate whether microRNA deregulation inhibits the regenerative potential of mesenchymal stromal cells and derived extracellular vesicles in a model of glycerol-induced AKI in severe combined immunodeficient mice. We generated mesenchymal stromal c  ...[more]

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