ROLE OF MIR-27A MEDIATED REGULATION OF VAV3 IN SEPSIS-INDUCED

Introduction: Despite recent advances in medicine, sepsis remains a disease with high mortality (30-50%). Of the many complications of sepsis, acute respiratory distress syndrome (ARDS) remains one of the most common and life-threatening illnesses. To date, there is no specific treatment for ARDS, and therapy is mainly supportive. Recent research show that mesenchymal stem cells (MSCs) have immunomodulatory and reparative potential in sepsis and ARDS (Mei et al. 2010), although the mechanism through which MSCs confer their beneficial effects is yet undetermined. To study the protective mechanisms of MSCs, we took interest in the growing field of study of microRNAs (miRs). MiRs are emerging as important post-transcriptional gene regulators in various diseases, and have potential of being novel therapeutic targets. We have identified miRs that are differentially expressed in septic lungs from MSC-treated vs non-treated mice, and generated a list of predicted targets for each miR. Particularly, miR-27a and its putative target gene VAV3 have been of interest. VAV3 is a guanine nucleotide exchange factor (GEF) for Rho family GTPases. It functions in a signaling pathway that alters actin structures, and thus has roles in cell migration.