Anti-apoptosis endothelial cell-secreted microRNA-195-5p promotes pulmonary arterial smooth muscle cell proliferation and migration in pulmonary arterial hypertension.
J Cell Biochem
; 119(2): 2144-2155, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-28862358
ABSTRACT
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 24 h, AR/PVECs had a higher mature miR-195-5p level than PVECs (P < 0.05, 12 and 24 h). 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-ß1-induced PASMCs remodeling. TGF-ß1 promoted cell growth in PASMCs, and the supernatant of PVECs/AP infected with Lv-S195 inhibited TGF-ß1 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Miócitos de Músculo Liso
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MicroRNAs
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Hipertensão Pulmonar
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Músculo Liso Vascular
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Cell Biochem
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China