MicroRNA Profiling in Experimental Sepsis-induced Acute Lung Injury

Introduction: Currently, there are no specific pharmacological treatments for sepsis-induced acute respiratory distress syndrome (ARDS). And mesenchymal stem cells (MSCs) have shown reparative potential in both sepsis and ARDS. Objectives: To determine the role of MSC administration in the modulation of pulmonary host-responses to sepsis via differential regulation of regulatory microRNAs (miRNAs/miRs). Methods: MicroRNA and mRNA profiling was performed to identify differential expression. Quantitative real time polymerase chain reaction (qRT-PCR), trans-endothelial electrical resistance (TEER) measurements, and luciferase activity assay were used. Results: MicroRNA expression was examined in Human Pulmonary Microvascular Endothelial Cells (HPMECs). One miRNA – miR-193b-5p, targets occludin, a tight junction protein associated with endothelial leakage. A specific regulatory relationship between miR-193b-5p and occludin was identified. The loss in endothelial integrity was rescued when miR-193b-5p inhibitor was transfected. Conclusion: miR-193b-5p is a suppressor of occludin. Studying transcriptional changes allows identification of therapeutically relevant mediators for ARDS/ALI treatment.MAS