ArticleRedox biology2019
Nox1/Ref-1-mediated activation of CREB promotes Gremlin1-driven endothelial cell proliferation and migration.
Article in Redox biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 64 citations in OpenAlex.
- Article
- Nutrient-Derived Modulation of the Gremlin-1/BMP-4 Axis by White Tea Preserves Insulin Sensitivity During Early Diet-Induced Metabolic Dysregulation.International journal of molecular sciences · 2026Article
- Mechanisms Underlying Altitude-Induced and Group 3 Pulmonary Hypertension.International journal of molecular sciences · 2026Review
- Caffeine improves diethylnitrosamine-induced hepatocellular carcinoma by inhibiting cAMP/PKA/CREB signaling in rats.Biochemistry and biophysics reports · 2025Article
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Ref-1 redox activity modulates canonical Wnt signaling in endothelial cells.Redox biology · 2025Article
- Associations of cathepsins with pulmonary arterial hypertension mediated by circulating metabolites: A Mendelian randomization study.Medicine · 2025Article
- PABPN1 functions as a downstream gene of CREB to inhibit the proliferation of preadipocytes.Animal bioscience · 2025Article
- Increased Neutrophil HResearch square · 2024Article
- Adipokines in pulmonary hypertension: angels or demons?Heliyon · 2023Review
- NADPH Oxidases: From Molecular Mechanisms to Current Inhibitors.Journal of medicinal chemistry · 2023Review
- Targeting oxidative stress as a preventive and therapeutic approach for cardiovascular disease.Journal of translational medicine · 2023Review
- Indirect Antioxidant Effects of the Nitrite Anion: Focus on Xanthine Oxidase.Advances in redox research · 2023Article
- Specificity Protein 1-Mediated Promotion of CXCL12 Advances Endothelial Cell Metabolism and Proliferation in Pulmonary Hypertension.Antioxidants (Basel, Switzerland) · 2022Article
- Expression of CD70 Modulates Nitric Oxide and Redox Status in Endothelial Cells.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- NADPH oxidase family proteins: signaling dynamics to disease management.Cellular & molecular immunology · 2022Review
- Modulating the Antioxidant Response for Better Oxidative Stress-Inducing Therapies: How to Take Advantage of Two Sides of the Same Medal?Biomedicines · 2022Review
- Nano-titanium dioxide inhalation exposure during gestation drives redox dysregulation and vascular dysfunction across generations.Particle and fibre toxicology · 2022Article
- Cooperation between CYB5R3 and NOX4 via coenzyme Q mitigates endothelial inflammation.Redox biology · 2021Article
- Zinc-mediated activation of CREB pathway in proliferation of pulmonary artery smooth muscle cells in pulmonary hypertension.Cell communication and signaling : CCS · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Pulmonary arterial hypertension (PAH) is a complex degenerative disorder marked by aberrant vascular remodeling associated with hyperproliferation and migration of endothelial cells (ECs). Previous reports implicated bone morphogenetic protein antagonist Gremlin 1 in this process; however, little is known of the molecular mechanisms involved. The current study was designed to test whether redox signaling initiated by NADPH oxidase 1 (Nox1) could promote transcription factor CREB activation by redox factor 1 (Ref-1), transactivation of Gremlin1 transcription, EC migration, and proliferation. Human pulmonary arterial EC (HPAECs) exposed in vitro to hypoxia to recapitulate PAH signaling displayed induced Nox1 expression, reactive oxygen species (ROS) production, PKA activity, CREB phosphorylation, and CREB:CRE motif binding. These responses were abrogated by selective Nox1 inhibitor NoxA1ds and/or siRNA Nox1. Nox1-activated CREB migrated to the nucleus and bound to Ref-1 leading to CREB:CRE binding and Gremlin1 transcription. CHiP assay and CREB gene-silencing illustrated that CREB is pivotal for hypoxia-induced Gremlin1, which, in turn, stimulates EC proliferation and migration. In vivo, participation of Nox1, CREB, and Gremlin1, as well as CREB:CRE binding was corroborated in a rat PAH model. Activation of a previously unidentified Nox1-PKA-CREB/Ref-1 signaling pathway in pulmonary endothelial cells leads to Gremlin1 transactivation, proliferation and migration. These findings reveal a new signaling pathway by which Nox1 via induction of CREB and Gremlin1 signaling contributes to vascular remodeling and provide preclinical indication of its significance in PAH.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.