A Regulatory miRNA-mRNA Network Is Associated with Tissue Repair Induced by Mesenchymal Stromal Cells in Acute Kidney Injury

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de Almeida, Danilo Candido ; Bassi, Enio Jose ; Azevedo, Hatylas ; Anderson, Leticia ; Taemi Origassa, Clarice Silvia ; Cenedeze, Marcos Antonio ; de Andrade-Oliveira, Vinicius ; Ferreira Felizardo, Raphael Jose ; da Silva, Reinaldo Correia ; Hiyane, Meire Ioshie ; Semedo, Patricia ; dos Reis, Marlene Antonia ; Moreira-Filho, Carlos Alberto ; Verjovski-Almeida, Sergio ; Pacheco-Silva, Alvaro ; Saraiva Camara, Niels Olsen

• Document type: Journal article
• Source: FRONTIERS IN IMMUNOLOGY; v. 7, JAN 3 2017.
• Web of Science Citations: 9

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-beta 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. (AU)

• FAPESP's process: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants