Niclosamide modulates phenotypic switch and inflammatory responses in human pulmonary arterial smooth muscle cells
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View abstract on PubMed
Summary
This summary is machine-generated.Niclosamide (NCL) effectively inhibits pulmonary arterial smooth muscle cell proliferation and migration, key factors in pulmonary arterial hypertension (PAH). This repurposed drug also reduces inflammation, suggesting potential as a novel PAH treatment.
Area Of Science
- Cardiovascular Biology
- Pharmacology
- Cell Biology
Background
- Pulmonary arterial smooth muscle cell (PASMC) proliferation and migration are central to pulmonary vascular remodeling in pulmonary arterial hypertension (PAH).
- Niclosamide (NCL), an anthelmintic, regulates cellular processes but its effects on PASMC phenotype and inflammation in PAH are unknown.
Purpose Of The Study
- To investigate the effects of Niclosamide (NCL) on pulmonary arterial smooth muscle cell (PASMC) proliferation, migration, phenotypic switch, and inflammatory responses.
- To explore the potential of repurposing Niclosamide (NCL) as a therapeutic agent for pulmonary arterial hypertension (PAH).
Main Methods
- Cell proliferation assays, flow cytometry, scratch wound, and transwell assays were used to assess PASMC proliferation and migration.
- Western blot analysis was employed to evaluate protein expression related to cell cycle, phenotype, signaling pathways (P38/STAT3), and inflammation (VCAM-1, ICAM-1, NLRP3 inflammasome).
- Macrophage adhesion assays were conducted to examine the impact of NCL on inflammatory cell recruitment.
Main Results
- Niclosamide (NCL) significantly inhibited PDGF-BB-induced PASMC proliferation and migration in a dose-dependent manner.
- NCL promoted G1 phase arrest and apoptosis in PASMCs, while restoring smooth muscle cell phenotype markers (SMA, SM22, calponin).
- NCL suppressed TNFα-induced inflammatory responses by reducing macrophage adhesion, VCAM-1/ICAM-1 expression, and inhibiting NLRP3 inflammasome activation.
Conclusions
- Niclosamide (NCL) exhibits multifaceted effects on PASMCs, controlling proliferation, migration, phenotypic switching, and inflammation.
- These findings suggest that Niclosamide (NCL) holds significant promise as a repurposed therapeutic strategy for treating pulmonary arterial hypertension (PAH).
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