title: A Regulatory miRNA-mRNA Network Is Associated with Tissue Repair Induced by Mesenchymal Stromal Cells in Acute Kidney Injury.
abstract: Mesenchymal stromal cells (MSCs) orchestrate tissue repair by releasing cell-derived microvesicles (MVs), which, presumably by small RNA species, modulate global gene expression. The knowledge of miRNA/mRNA signatures linked to a reparative status may elucidate some of the molecular events associated with MSC protection. Here, we used a model of cisplatin-induced kidney injury (acute kidney injury) to assess how MSCs or MVs could restore tissue function. MSCs and MVs presented similar protective effects, which were evidencedin vivoandin vitroby modulating apoptosis, inflammation, oxidative stress, and a set of prosurvival molecules. In addition, we observed that miRNAs (i.e., miR-880, miR-141, miR-377, and miR-21) were modulated, thereby showing active participation on regenerative process. Subsequently, we identified that MSC regulates a particular miRNA subset which mRNA targets are associated with Wnt/TGF-β, fibrosis, and epithelial-mesenchymal transition signaling pathways. Our results suggest that MSCs release MVs that transcriptionally reprogram injured cells, thereby modulating a specific miRNA-mRNA network.
authors.affiliation: Departamento de Medicina, Divisão de Nefrologia, Universidade Federal de São Paulo, São Paulo, Brazil; Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Danilo Candido
authors.initials: DC
authors.lastname: de Almeida
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil; Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Alagoas, Maceió, Brazil.
authors.forename: Ênio Jose
authors.initials: ÊJ
authors.lastname: Bassi
authors.affiliation: Departamento de Pediatria, Faculdade de Medicina, Universidade de São Paulo , São Paulo , Brazil.
authors.forename: Hatylas
authors.initials: H
authors.lastname: Azevedo
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil; Instituto Butantan, São Paulo, Brazil.
authors.forename: Letícia
authors.initials: L
authors.lastname: Anderson
authors.affiliation: Departamento de Medicina, Divisão de Nefrologia, Universidade Federal de São Paulo , São Paulo , Brazil.
authors.forename: Clarice Silvia Taemi
authors.initials: CS
authors.lastname: Origassa
authors.affiliation: Departamento de Medicina, Divisão de Nefrologia, Universidade Federal de São Paulo , São Paulo , Brazil.
authors.forename: Marcos Antônio
authors.initials: MA
authors.lastname: Cenedeze
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo , São Paulo , Brazil.
authors.forename: Vinicius
authors.initials: V
authors.lastname: de Andrade-Oliveira
authors.affiliation: Departamento de Medicina, Divisão de Nefrologia, Universidade Federal de São Paulo , São Paulo , Brazil.
authors.forename: Raphael José Ferreira
authors.initials: RJ
authors.lastname: Felizardo
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo , São Paulo , Brazil.
authors.forename: Reinaldo Correia
authors.initials: RC
authors.lastname: da Silva
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo , São Paulo , Brazil.
authors.forename: Meire Ioshie
authors.initials: MI
authors.lastname: Hiyane
authors.affiliation: Departamento de Medicina, Divisão de Nefrologia, Universidade Federal de São Paulo , São Paulo , Brazil.
authors.forename: Patricia
authors.initials: P
authors.lastname: Semedo
authors.affiliation: Departamento de Patologia, Universidade Federal do Triângulo Mineiro , Uberaba , Brazil.
authors.forename: Marlene Antônia
authors.initials: MA
authors.lastname: Dos Reis
authors.affiliation: Departamento de Pediatria, Faculdade de Medicina, Universidade de São Paulo , São Paulo , Brazil.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Moreira-Filho
authors.affiliation: Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil; Instituto Butantan, São Paulo, Brazil.
authors.forename: Sergio
authors.initials: S
authors.lastname: Verjovski-Almeida
authors.affiliation: Departamento de Medicina, Divisão de Nefrologia, Universidade Federal de São Paulo , São Paulo , Brazil.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Pacheco-Silva
authors.affiliation: Departamento de Medicina, Divisão de Nefrologia, Universidade Federal de São Paulo, São Paulo, Brazil; Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Niels Olsen Saraiva
authors.initials: NO
authors.lastname: Câmara
keywords: cellular reprograming; gene expression; mesenchymal stromal cells; miRNAs; microvesicles