AUTHOR=de Almeida Danilo Candido , Bassi Ênio Jose , Azevedo Hatylas , Anderson Letícia , Origassa Clarice Silvia Taemi , Cenedeze Marcos Antônio , Andrade-Oliveira Vinicius de , Felizardo Raphael José Ferreira , Silva Reinaldo Correia da , Hiyane Meire Ioshie , Semedo Patricia , Reis Marlene Antônia dos , Moreira-Filho Carlos Alberto , Verjovski-Almeida Sergio , Pacheco-Silva Álvaro , Câmara Niels Olsen Saraiva TITLE=A Regulatory miRNA–mRNA Network Is Associated with Tissue Repair Induced by Mesenchymal Stromal Cells in Acute Kidney Injury JOURNAL=Frontiers in Immunology VOLUME=7 YEAR=2017 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00645 DOI=10.3389/fimmu.2016.00645 ISSN=1664-3224 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 evidenced in vivo and in vitro by 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.