miR-27a promotes endothelial-mesenchymal transition in hypoxia-induced pulmonary arterial hypertension by suppressing BMP signaling

This study was designed to investigate the role and underlying mechanism of miR-27a in EndMT during PAH.Main methodsRats were exposed in hypoxia (10% O2) for 3 weeks to induce PAH, and human pulmonary artery endothelial cells (HPAECs) were exposed in hypoxia (1% O2) for 48 h to induce EndMT. Immunohistochemistry, in situ hybridization, immunofluorescence, real-time PCR and Western blot were conducted to detect the expressions of RNAs and proteins, and luciferase assay was used to verify the putative binding site of miR-27a.Key findingsWe found that hypoxia up-regulated miR-27a in the tunica intima of rat pulmonary arteries and HPAECs, and that inhibition of miR-27a suppressed hypoxia-induced EndMT. Furthermore, elevated expression of miR-27a suppressed bone morphogenetic protein (BMP) signaling by targeting Smad5, thereby lessening Id2-mediated repression of the 2 critical mediators of EndMT (Snail and Twist).SignificanceOur data unveiled a novel role of miR-27a in EndMT during hypoxia-induced PAH. Thus, targeting of miR-27a-related pathway may be therapeutically harnessed to treat PAH.

Source: Life Sciences - April 17, 2019 Category: Biology Source Type: research