Overexpressed microRNA-615-3p promotes progression of neonatal acute respiratory distress syndrome by inhibiting differentiation of mesenchymal stem cells to alveolar type II epithelial cells

摘要

OBJECTIVE: To explore whether microRNA-615-3p participates in the progression of neonatal acute respiratory distress syndrome (ARDS) by inhibiting differentiation of mesenchymal stem cells (MSCs) to alveolar type II epithelial cells (ATII) via Wnt/β-catenin pathway. PATIENTS AND METHODS: Expression levels of microRNA-615-3p and inflammatory factors (IL-1, IL-6, IL-8, and TNF-α) in peripheral blood of 24 neonatal ARDS patients and 14 healthy newborns were detected by qRT-PCR (quantitative Real-Time Polymerase Chain Reaction). MSCs were isolated from bone marrow of mice and identified by flow cytometry. The effect of microRNA-615-3p on regulating the differentiation of MSCs to ATII was analyzed. After altering expressions of microRNA-615-3p and DKK1 by plasmids transfection, Wnt/β-catenin pathway-related genes were detected by Western blot. RESULTS: Higher expression levels of microRNA-615-3p and inflammatory factors (IL-1, IL-6, IL-8, and TNF-α) were observed in peripheral blood of neonatal ARDS patients than those of healthy newborns. ATII-specific genes were upregulated, and inflammatory factors were downregulated after the microRNA-615-3p knockdown in MSCs. Moreover, expressions of Wnt/β-catenin pathway-related genes were downregulated after the microRNA-615-3p overexpression, which was partially reserved by the DKK1 knockdown. CONCLUSIONS: Overexpressed microRNA-615-3p promoted ARDS development through inhibiting differentiation of MSCs to ATII via Wnt/β-catenin pathway.