ArticlePloS one2014
NOX4 mediates BMP4-induced upregulation of TRPC1 and 6 protein expressions in distal pulmonary arterial smooth muscle cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- The odyssey of the TR(i)P journey to the cellular membrane.Frontiers in cell and developmental biology · 2024Review
- Airway Smooth Muscle Regulated by Oxidative Stress in COPD.Antioxidants (Basel, Switzerland) · 2023Review
- Inflammation and Nitro-oxidative Stress as Drivers of Endocannabinoid System Aberrations in Mood Disorders and Schizophrenia.Molecular neurobiology · 2022Review
- Crucial Role of Stromal Interaction Molecule-Activated TRPC-ORAI Channels in Vascular Remodeling and Pulmonary Hypertension Induced by Intermittent Hypoxia.Frontiers in physiology · 2022Article
- Nox4 Maintains Blood Pressure during Low Sodium Diet.Antioxidants (Basel, Switzerland) · 2021Article
- Cellular Pathways Promoting Pulmonary Vascular Remodeling by Hypoxia.Physiology (Bethesda, Md.) · 2020Review
- Regulation of Smooth Muscle Cell Proliferation by NADPH Oxidases in Pulmonary Hypertension.Antioxidants (Basel, Switzerland) · 2019Review
- Therapeutic potential of NADPH oxidase 1/4 inhibitors.British journal of pharmacology · 2017Review
- Critical role of X-box binding protein 1 in NADPH oxidase 4-triggered cardiac hypertrophy is mediated by receptor interacting protein kinase 1.Cell cycle (Georgetown, Tex.) · 2017Article
- The Role of Transient Receptor Potential Channel 6 Channels in the Pulmonary Vasculature.Frontiers in immunology · 2017Review
- Bortezomib alleviates experimental pulmonary hypertension by regulating intracellular calcium homeostasis in PASMCs.American journal of physiology. Cell physiology · 2016Article
- NADPH oxidases-do they play a role in TRPC regulation under hypoxia?Pflugers Archiv : European journal of physiology · 2016Review
- Calcium and ROS: A mutual interplay.Redox biology · 2015Review
- Inactivation of carboxyl terminus of Hsc70-interacting protein prevents hypoxia-induced pulmonary arterial smooth muscle cells proliferation by reducing intracellular CaPulmonary circulationArticle
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
rationaleOur previous studies demonstrated that bone morphogenetic protein 4 (BMP4) mediated, elevated expression of canonical transient receptor potential (TRPC) largely accounts for the enhanced proliferation in pulmonary arterial smooth muscle cells (PASMCs). In the present study, we sought to determine the signaling pathway through which BMP4 up-regulates TRPC expression.
methodsWe employed recombinant human BMP4 (rhBMP4) to determine the effects of BMP4 on NADPH oxidase 4 (NOX4) and reactive oxygen species (ROS) production in rat distal PASMCs. We also designed small interfering RNA targeting NOX4 (siNOX4) and detected whether NOX4 knockdown affects rhBMP4-induced ROS, TRPC1 and 6 expression, cell proliferation and intracellular Ca2+ determination in PASMCs.
resultsIn rhBMP4 treated rat distal PASMCs, NOX4 expression was (226.73±11.13) %, and the mean ROS level was (123.65±1.62) % of that in untreated control cell. siNOX4 transfection significantly reduced rhBMP4-induced elevation of the mean ROS level in PASMCs. Moreover, siNOX4 transfection markedly reduced rhBMP4-induced elevation of TRPC1 and 6 proteins, basal [Ca2+]i and SOCE. Furthermore, compared with control group (0.21±0.001), the proliferation of rhBMP4 treated cells was significantly enhanced (0.41±0.001) (P<0.01). However, such increase was attenuated by knockdown of NOX4. Moreover, external ROS (H2O2 100 µM, 24 h) rescued the effects of NOX4 knockdown, which included the declining of TRPC1 and 6 expression, basal intracellular calcium concentration ([Ca2+]i) and store-operated calcium entry (SOCE), suggesting that NOX4 plays as an important mediator in BMP4-induced proliferation and intracellular calcium homeostasis.
conclusionThese results suggest that BMP4 may increase ROS level, enhance TRPC1 and 6 expression and proliferation by up-regulating NOX4 expression in PASMCs.
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