MiR-23a regulates the proliferation and migration of human pulmonary artery smooth muscle cells (HPASMCs) through targeting BMPR2/Smad1 signaling.

Pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) (PAH-CHD) is a severe and progressive disease with a poor prognosis. MiR-23a, a member of miR-23a/24/27a cluster, has been reported to function as an important player in PAH. However, the detailed functions and molecular mechanisms of miR-23a in PAH-CHD are still not fully elucidated. Due to hypoxia is an important stimulus for pulmonary artery smooth muscle cells (PASMCs) proliferation and vascular remodeling, we assessed the expression and functions of miR-23a in hypoxia-induced HPASMCs. qRT-PCR assay revealed that miR-23a level was upregulated in plasma of PAH-CHD patients and hypoxia-induced HPASMCs. Loss-of-function experiments demonstrated that miR-23a depletion suppressed hypoxia-induced proliferation and migration in HPASMCs. Dual-luciferase reporter assay verified that bone morphogenetic protein receptor type 2 (BMPR2) was a direct target of miR-23a. Moreover, BMPR2 level was downregulated in plasma of PAH-CHD patients and hypoxia-induced HPASMCs. Additionally, BMPR2-mediated suppression on proliferation and migration of hypoxia-induced HPASMCs was abrogated by miR-23a overexpression. Furthermore, miR-23a directly affected BMPR2/Smad1 signaling in hypoxia-induced HPASMCs. In conclusion, miR-23a facilitated cell proliferation and migration by targeting BMPR2/Smad1 signaling in hypoxia-induced HPASMCs, providing a potential therapeutic target for PAH treatment.
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