ArticleCardiovascular research2015
Hypoxia inducible factor-1-dependent up-regulation of BMP4 mediates hypoxia-induced increase of TRPC expression in PASMCs.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- Hypoxic microenvironment and pulmonary hypertension.Respiratory research · 2025Review
- Protective Role of TRPC3 Gene Polymorphism (rs10518289) in Obstructive Sleep Apnea Hypopnea Syndrome Among Hypertensive Patients.Medical science monitor : international medical journal of experimental and clinical research · 2024Article
- Hypoxia-Induced FUS-circTBC1D14 Stress Granules Promote Autophagy in TNBC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Hypermethylation of the Bmp4 promoter dampens binding of HIF-1α and impairs its cardiac protective effects from oxidative stress in prenatally GC-exposed offspring.Cellular and molecular life sciences : CMLS · 2023Article
- Bioactivities and mechanisms of natural medicines in the management of pulmonary arterial hypertension.Chinese medicine · 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
- The biology of bone morphogenetic protein signaling pathway in cerebrovascular system.Chinese neurosurgical journal · 2021Review
- Proteomic analysis of hypoxia and non-hypoxia secretome mesenchymal stem-like cells from human breastmilk.Saudi journal of biological sciences · 2021Article
- Androgens regulate ovarian gene expression by balancing Ezh2-Jmjd3 mediated H3K27me3 dynamics.PLoS genetics · 2021Article
- Histidine decarboxylase deficiency inhibits NBP-induced extramedullary hematopoiesis by modifying bone marrow and spleen microenvironments.International journal of hematology · 2021Article
- Mechanisms of vasculogenic mimicry in hypoxic tumor microenvironments.Molecular cancer · 2021Review
- Heart‑lung crosstalk in pulmonary arterial hypertension following myocardial infarction (Review).International journal of molecular medicine · 2020Review
- Review
- Cellular Pathways Promoting Pulmonary Vascular Remodeling by Hypoxia.Physiology (Bethesda, Md.) · 2020Review
- TRPC channels: Structure, function, regulation and recent advances in small molecular probes.Pharmacology & therapeutics · 2020Review
- Consecutive Hypoxia Decreases Expression ofFrontiers in cell and developmental biology · 2020Article
- Trpc1 as the Missing Link Between the Bmp and CaScientific reports · 2019Article
- HBioscience reports · 2019Article
- Generation of Vascular Networks from AdipocytesInternational journal of cell science & molecular biology · 2019Article
- SGK1 Mediates Hypoxic Pulmonary Hypertension through Promoting Macrophage Infiltration and Activation.Analytical cellular pathology (Amsterdam) · 2019Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
aimsPreviously we demonstrated that both hypoxia inducible factor-1 (HIF-1) and bone morphogenetic protein-4 (BMP4) up-regulate transient receptor potential canonical (TRPC) 1 and TRPC6, resulting in increased basal intracellular Ca(2+) concentration ([Ca(2+)]i) in pulmonary arterial smooth muscle cells (PASMCs), driving development of chronic hypoxia (CH)-induced pulmonary hypertension (CHPH). This study aims to determine whether HIF-1 regulates BMP4, and whether BMP4 mediates TRPC and basal [Ca(2+)]i increases in hypoxic PASMCs. METHODS AND
resultsThe level of BMP4 mature protein was increased for ∼183% in distal pulmonary arterial smooth muscle (PA) from CH (10% O2 for 21 days; CH) exposed rats, and 143% in PASMCs cultured under prolonged hypoxia (4% O2 for 60 h). In rat PASMCs, HIF-1α overexpression up-regulated, whereas HIF-1α knockdown under hypoxia decreased BMP4 expression; site-mutation identified two functional HIF-1-binding sites in Bmp4 gene promoter; noggin or BMP4 siRNA treatment blocked hypoxia-induced increases of TRPC1 and TRPC6 expression and basal [Ca(2+)]i. Likewise, in mice, exposure to CH increased BMP4 expression in distal PA for ∼80%, which was absent in HIF-1α heterozygous mutant mice. Comparing with wild-type littermates, BMP4 heterozygous mutant mice exposed to CH displayed lower BMP4 and TRPC levels in PA, decreased basal [Ca(2+)]i in PASMCs, and attenuated CHPH. In human PASMCs, HIF-1α knockdown attenuated hypoxia-induced BMP4 expression and knockdown of either HIF-1α or BMP4 abolished hypoxia-induced TRPC expression and basal [Ca(2+)]i.
conclusionsBMP4 acts downstream of HIF-1 and mediates hypoxia-induced up-regulation of TRPC, leading to increased basal [Ca(2+)]i in PASMCs, promoting CHPH pathogenesis.
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