MiR-199a-3p deficiency induced by STAT3 activation drives smooth muscle cell phenotypic switching in pulmonary arterial hypertension.

Authors

Wen-Xia He, Yun-Jie Huang, Tian-Hong Ai, Song-Qun Huang, Xiao-Hua You, Hong Wu, Xiao-Wei Song

Published in

Non-coding RNA research. Volume 20. Pages 44-56. Epub Jul 09, 2026.

Abstract

Pulmonary arterial hypertension (PAH) is a progressive vasculopathy characterized by pathological vascular remodeling, in which pulmonary artery smooth muscle cells (PASMCs) undergo phenotypic switching from a contractile to a synthetic state, driving excessive proliferation and migration. Here, we report that miR-199a-3p is significantly downregulated in both hypoxia/SU5416-induced PAH rat models and PDGF-BB-stimulated human PASMCs. Mechanistically, PDGF-BB stimulation induces the phosphorylation of STAT3, which directly binds to the TTCCCGGAA motif within the promoter of miR-199a-3p. This binding transcriptionally represses miR-199a-3p. Functional analyses demonstrated that miR-199a-3p overexpression maintains the PASMC contractile phenotype (upregulating MYH11 and SM22α) and suppresses proliferation and migration. Conversely, miR-199a-3p inhibition promotes synthetic phenotypic switching and activates the ERK/AKT signaling pathway. Furthermore, we identified YAP1 as a novel direct target of miR-199a-3p, linking miRNA downregulation to downstream proliferative signaling. Collectively, these findings establish a PDGF-BB/STAT3/miR-199a-3p/YAP1 regulatory axis that drives pathological PASMC phenotypic switching. This axis represents a promising therapeutic target for mitigating pulmonary vascular remodeling in PAH.

PMID:
42472221
Bibliographic data and abstract were imported from PubMed on 19 Jul 2026.

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