ArticleScientific reports2017
Inhibition of phosphodiesterase-5 suppresses calcineurin/NFAT- mediated TRPC6 expression in pulmonary artery smooth muscle cells.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- The critical role of NFAT transcription factors in pulmonary arterial remodeling and pulmonary hypertension: from PASMC proliferation to therapeutic targeting.Molecular biology reports · 2026Review
- Diverse effects of calcineurin in vascular smooth muscle cells: physiological activators and the controversial actions of clinical inhibitors.Frontiers in pharmacology · 2026Review
- NAMPT modulates muscle fiber type transition in PAD myopathy via the cGMP-PKG signaling pathway.Biology direct · 2025Article
- Review
- Calcineurin Is a Universal Regulator of Vessel Function-Focus on Vascular Smooth Muscle Cells.Cells · 2023Review
- METTL3 Promotes Endothelium-Mesenchymal Transition of Pulmonary Artery Endothelial Cells by Regulating TRPC6/Calcineurin/NFAT Signaling Pathways.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- Identification of dysregulated pathways underlying HTLV-1-associated myelopathy/tropical spastic paraparesis through co-expression network analysis.Journal of neurovirology · 2021Article
- Inhibition of calcineurin/NFATc4 signaling attenuates ventilator‑induced lung injury.Molecular medicine reports · 2020Article
- SIRT6 Suppresses NFATc4 Expression and Activation in Cardiomyocyte Hypertrophy.Frontiers in pharmacology · 2018Article
- SphK1/S1P mediates TGF-β1-induced proliferation of pulmonary artery smooth muscle cells and its potential mechanisms.Pulmonary circulationArticle
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The up-regulation of transient receptor potential channel 6 (TRPC6) has been found to contribute to the proliferation of pulmonary artery smooth muscle cells (PASMCs), and inhibition of phosphodiesterase-5 (PDE5) has been shown to suppress TRPC6 expression in PASMCs. However, the molecular mechanisms underlying the up-regulation of TRPC6 expression and PDE5 modulation of TRPC6 expression in PASMCs remain largely unclear. The aim of this study is to address these issues. Endothelin-1 (ET-1) dose and time-dependently up-regulated TRPC6 expression in primary cultured rat PASMCs, and this was accompanied with the activation of calcineurin and subsequent translocation of NFATc4 to the nucleus. Further study indicated that inhibition of calcineurin by cyclosporine A or knockdown of NFATc4 using small interfering RNA suppressed ET-1-induced TRPC6 up-regulation. In addition, luciferase reporter assay showed that NFATc4 directly regulated the expression of TRPC6 in PASMCs. Inhibition of PDE5 by sildenafil suppressed ET-1-induced activation of calcineurin/NFATc4 signaling pathway and consequent TRPC6 up-regulation in PASMCs, while these inhibitory effects of sildenafil were abolished by PKG inhibitor Rp-8Br-cGMPs. Taken together, our study indicates that ET-1 stimulates TRPC6 expression by activation of calcineurin/NFATc4 signaling pathway, and inhibition of PDE5 suppresses calcineurin/NFATc4- mediated TRPC6 expression in PASMCs in a cGMP-PKG-dependent manner.
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