Anti-apoptosis endothelial cell-secreted microRNA-195-5p promotes pulmonary arterial smooth muscle cell proliferation and migration in pulmonary arterial hypertension

作者：Zeng, Zhen^*; Yao, Jun; Li, Yinchuan; Xue, Ying; Zou, Yinghua; Shu, Zhuoling; Jiao, Zhihua

来源：Journal of Cellular Biochemistry, 2018, 119(2): 2144-2155.

DOI：10.1002/jcb.26376

• apoptosis-resistant pulmonary endothelial cells
• microRNAs
• pulmonary arterial hypertension
• pulmonary vascular remodeling

In the pathological mechanism of pulmonary arterial hypertension, the role of apoptosis-resistant pulmonary microvascular endothelial cells (PVECs/AR) has been emphasized on the pulmonary vascular remodeling. In the present study, we investigated whether PVECs/AR can promote the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs), and to study the role of miR-195-5p in the crosstalk between these two types of cells. We confirmed that PVECs/AR can promote the proliferation and migration of PASMCs in a co-culture system of AR/PVECs and PASMCs. Additionally, after exposure to hypoxia for 12 or 24h, AR/PVECs had a higher mature miR-195-5p level than PVECs (P<0.05, 12 and 24h). Luciferase reporter assays were used to validate indications of the existence of an HRE in the miR-195-5p promoter. Knocking down Smad7 can reverse the inhibition of Lv-S195 on TGF-1-induced PASMCs remodeling. TGF-1 promoted cell growth in PASMCs, and the supernatant of PVECs/AP infected with Lv-S195 inhibited TGF-1 enhanced proliferation in PASMCs, which was also blocked by Lv-shRNA-Smad7. The result of this experiment confirmed the specificity of the HIF-1a/miR-195/Smad7 pathway. Our data indicate the possible function of PVECs/AR in the process of pulmonary vascular remodeling. MiRNA-195-5p played a role as an interacting paracrine factor between PVECs/AR and PASMC, which seemed to function through the HIF-1a/miRNA-195-5p/Smad7 pathway.

• 出版日期2018-2
• 单位上海交通大学