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MYNN regulates hypoxia-induced PASMCs proliferation and migration by modulating the PDLIM1/NF-κB axis
Xinmeng Guo1, Chao Gao1, Lingxue Li1
1Department of Medical Biology, Harbin Medical University, Daqing Campus, P.R. China.
European Journal of Pharmacology
|August 5, 2026
Summary
Myoneurin (MYNN) acts as a protective factor in pulmonary arterial hypertension (PAH). It suppresses smooth muscle cell proliferation by regulating the PDLIM1/NF-κB pathway, offering a potential therapeutic target for PAH.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Cellular Physiology
Background:
- Pulmonary arterial hypertension (PAH) involves abnormal proliferation and migration of pulmonary artery smooth muscle cells (PASMCs).
- The precise molecular mechanisms driving PASMC dysfunction in PAH remain incompletely understood.
- Identifying novel regulatory factors is crucial for developing effective PAH therapies.
Purpose of the Study:
- To investigate the role of the transcription factor myoneurin (MYNN) in the pathogenesis of PAH.
- To elucidate the molecular mechanism by which MYNN influences PASMC behavior.
- To explore MYNN as a potential therapeutic target for PAH.
Main Methods:
- In vitro studies using human and mouse PASMCs under normoxic and hypoxic conditions.
- Gene expression analysis of MYNN and PDLIM1.
- Functional assays including cell proliferation and migration.
- Luciferase reporter assays to confirm promoter binding and transcriptional regulation.
- Western blotting to assess protein levels, including NF-κB activation.
Main Results:
- Hypoxia reduced MYNN expression in PASMCs.
- MYNN knockdown enhanced PASMC proliferation and migration, while MYNN overexpression suppressed these processes.
- MYNN directly binds to the PDLIM1 promoter, increasing its transcription.
- Reduced MYNN led to decreased PDLIM1, releasing inhibition on NF-κB and promoting PASMC pathology.
- A novel MYNN/PDLIM1/NF-κB signaling axis was identified.
Conclusions:
- MYNN acts as a protective transcription factor in PAH pathogenesis.
- The MYNN/PDLIM1/NF-κB signaling pathway is critical in hypoxia-induced PASMC proliferation and migration.
- Targeting MYNN represents a promising therapeutic strategy for pulmonary arterial hypertension.
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