PDGFBB promotes proliferation and migration via regulating miR-1181/STAT3 axis in human pulmonary arterial smooth muscle cells.
Am J Physiol Lung Cell Mol Physiol
; 315(6): L965-L976, 2018 12 01.
Article
en En
| MEDLINE
| ID: mdl-30211651
ABSTRACT
Platelet-derived growth factor (PDGF) can induce hyperproliferation of pulmonary artery smooth muscle cells (PASMCs), which is a key causative factor to the occurrence and progression of pulmonary arterial hypertension (PAH). We previously identified that miR-1181 is significantly downregulated by PDGFBB in human PASMCs. In this work, we further explore the function of miR-1181 and underlying regulatory mechanisms in PDGF-induced PASMCs. First, the expression pattern of miR-1181 was characterized under PDGFBB treatment, and PDGF receptor/PKCß signaling was found to repress miR-1181 expression. Then, gain- and loss-of-function experiments were respectively conducted and revealed the prominent role of miR-1181 in inhibiting PASMC proliferation and migration. Flow cytometry analysis suggested that miR-1181 regulated the PASMC proliferation through influencing the cell cycle transition from G0/G1 to S phase. Moreover, we exhibited that miR-1181 targeting STAT3 formed a regulatory axis to modulate PASMC proliferation. Finally, serum miR-1181 expression was also observed to be reduced in adult and newborn patients with PAH. Overall, this study provides novel findings that the miR-1181/STAT3 axis mediated PDGFBB-induced dysfunction in human PASMCs, implying a potential use of miR-1181 as a therapeutic and diagnostic candidate for the vascular remodeling diseases.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Arteria Pulmonar
/
Miocitos del Músculo Liso
/
MicroARNs
/
Proliferación Celular
/
Factor de Transcripción STAT3
/
Becaplermina
/
Músculo Liso Vascular
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Am J Physiol Lung Cell Mol Physiol
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FISIOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
China