MYNN regulates hypoxia-induced PASMCs proliferation and migration by modulating the PDLIM1/NF-κB axis.

This study aimed to investigate the role and mechanism of the transcription factor myoneurin (MYNN) in the pathogenesis of pulmonary arterial hypertension (PAH). In vitro, hypoxia-treated human and mouse pulmonary artery smooth muscle cells (PASMCs) exhibited reduced MYNN expression. Functional studies demonstrated that knockdown of MYNN promoted the proliferation and migration of PASMCs under normoxic conditions, whereas overexpression of MYNN effectively suppressed hypoxia-induced abnormal proliferation and migration of PASMCs. Mechanistically, MYNN directly binds to the promoter region of the PDLIM1 gene and promotes its transcription. Downregulation of MYNN led to decreased PDLIM1 expression, thereby releasing the inhibition on NF-κB and ultimately driving the pathological proliferation and migration of PASMCs. This study reveals MYNN/PDLIM1/NF-κB signaling axis in hypoxia induced PASMC proliferation and migration, and establishes MYNN functions as a protective transcription factor, thereby revealing a promising new therapeutic approach for PAH.