ArticleInternational journal of molecular sciences2021
Adenylate Kinase 4-A Key Regulator of Proliferation and Metabolic Shift in Human Pulmonary Arterial Smooth Muscle Cells via Akt and HIF-1α Signaling Pathways.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Bellidifolin Improves Pulmonary Artery Smooth Muscle Cells Proliferation by Targeting the IGFBP5-Mediated PI3K-AKT-mTOR Pathway and Dilates the Pulmonary Artery.Biomolecules · 2026Article
- Energy Homeostasis Disruption in Neurological Disorders: Mitochondrial Dysfunction, High-Energy Phosphate Transfer, and Extracellular ATP-Dependent Purinergic Dysregulation.International journal of molecular sciences · 2026Review
- Hsa_circ_0005372 function as both sponging miR-877-3p and interacting with RNA binding proteins DNMT1 to promote proliferation of human pulmonary smooth muscle cells.Translational pediatrics · 2026Article
- The effect of mitoTEMPO on the development of hypoxia-induced pulmonary hypertension in male mice.Physiological reports · 2026Article
- The Effect of Training on the Expression of Protein and Metabolites in the Plasma Exosomes of theAnimals : an open access journal from MDPI · 2026Article
- Multiomics Analysis of Nucleotide Metabolism Highlights the Important Role of Adenylate Kinase 4 in Pancreatic Cancer.Human mutation · 2026Article
- Inhibiting the pathological changes of PASMCs is an effective approach for medicinal plants or secondary metabolites in treating pulmonary hypertension.Frontiers in pharmacology · 2026Review
- The impact of hypoxia on the cellular phenotype and proteome of KGN cells.Reproduction & fertility · 2025Article
- Circ-06958 Is Involved in Meat Quality by Regulating Cell Proliferation Through miR-31-5p/AK4 Axis in Pigs.Cells · 2025Article
- Natural products targeting the immune-metabolic regulatory network in pulmonary hypertension: mechanisms, classification, and therapeutic prospects.Frontiers in pharmacology · 2025Review
- Glycolysis modulation: New therapeutic strategies to improve pulmonary hypertension (Review).International journal of molecular medicine · 2024Review
- Crosstalk of methylation and tamoxifen in breast cancer (Review).Molecular medicine reports · 2024Review
- Transcriptional Responses of Different Brain Cell Types to Oxygen Decline.Brain sciences · 2024Article
- Mitochondrial influences on smooth muscle phenotype.American journal of physiology. Cell physiology · 2024Review
- Pulmonary Hypertension: Unveiling Molecular Mechanisms, Diagnosis, and Therapeutic Targets.Journal of personalized medicine · 2023Article
- Evidence for Hypoxia-Induced Shift in ATP Production from Glycolysis to Mitochondrial Respiration in Pulmonary Artery Smooth Muscle Cells in Pulmonary Arterial Hypertension.Journal of clinical medicine · 2023Article
- Regulation of Adenine Nucleotide Metabolism by Adenylate Kinase Isozymes: Physiological Roles and Diseases.International journal of molecular sciences · 2023Review
- Pulmonary Vascular Remodeling in Pulmonary Hypertension.Journal of personalized medicine · 2023Review
- SPOC domain-containing protein 1 regulates the proliferation and apoptosis of human spermatogonial stem cells through adenylate kinase 4.World journal of stem cells · 2022Article
- Association of AK4 Protein From Stem Cell-Derived Neurons With Cognitive Reserve: An Autopsy Study.Neurology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Increased proliferation of pulmonary arterial smooth muscle cells (PASMCs) in response to chronic hypoxia contributes to pulmonary vascular remodeling in pulmonary hypertension (PH). PH shares numerous similarities with cancer, including a metabolic shift towards glycolysis. In lung cancer, adenylate kinase 4 (AK4) promotes metabolic reprogramming and metastasis. Against this background, we show that AK4 regulates cell proliferation and energy metabolism of primary human PASMCs. We demonstrate that chronic hypoxia upregulates AK4 in PASMCs in a hypoxia-inducible factor-1α (HIF-1α)-dependent manner. RNA interference of AK4 decreases the viability and proliferation of PASMCs under both normoxia and chronic hypoxia. AK4 silencing in PASMCs augments mitochondrial respiration and reduces glycolytic metabolism. The observed effects are associated with reduced levels of phosphorylated protein kinase B (Akt) as well as HIF-1α, indicating the existence of an AK4-HIF-1α feedforward loop in hypoxic PASMCs. Finally, we show that AK4 levels are elevated in pulmonary vessels from patients with idiopathic pulmonary arterial hypertension (IPAH), and AK4 silencing decreases glycolytic metabolism of IPAH-PASMCs. We conclude that AK4 is a new metabolic regulator in PASMCs interacting with HIF-1α and Akt signaling pathways to drive the pro-proliferative and glycolytic phenotype of PH.
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Registered trials
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.