The protective effects of MSC-EXO against pulmonary arterial hypertension through inhibition of Wnt/BMP signaling pathway

Background: The aim of the study was to explore the mechanism of mesenchymal human umbilical cord msenchymal stem cells derived exosomes (MSC-EXO) against experimental pulmonary artery hypertension (PAH) pulmonary vascular remodeling . Methods and results After PAH model was successful established, the animals received tail vein injections of MSC-EXO. Post-operation, the pulmonary artery pressure was measured, and the lung tissues were stained to evaluate the pulmonary vascular remodeling. Our results showed that MSC-EXO could significantly inhibit the pulmonary arterial hypertension, attenuate pulmonary vascular remodeling and lung fibrosis in vivo . Furthermore, the hypoxia-induced pulmonary artery endothelial cell (PAEC) model was used in vitro . Our results showed the expression of CD31, V-Ecadherin, Wnt5a, Wnt11, BMPR2 and Smad1/5/8 were significantly higher, but the expression of alpha smooth muscle actin (a-SMA), β-catenin, cyclin D1 and Smad2/3 were significantly lower in in MSC-EXO administration group then that in MCT or hypoxia group. Moreover, the present study found that BMP signaling suppressed obviously when the cells were transfection with Wnt5a siRNA. Conclusion In conclusion, these results suggested that MSC-EXO could protect PAH vascular remodeling through regulation of Wnt/BMP signaling pathway.