ArticleThe American journal of the medical sciences2016
Time-dependent PPARγ Modulation of HIF-1α Signaling in Hypoxic Pulmonary Artery Smooth Muscle Cells.
Article in The American journal of the medical sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Inhibition of fatty acid-binding protein 4 alleviates psoriasis-like skin inflammation by modulating macrophage polarization.Frontiers in immunology · 2026Article
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- BCR::ABL1 expression in chronic myeloid leukemia cells in low oxygen is regulated by glutamine via CD36-mediated fatty acid uptake.Cancer cell international · 2025Article
- The impact of high altitude (hypobaric hypoxia) on insulin resistance in humans.Journal of physiology and biochemistry · 2025Review
- Hyperoxia as a driver of gut dysbiosis.Frontiers in microbiology · 2025Review
- Sex hormone binding globulin (SHBG) modulates mitochondrial dynamics in PPARγ-depleted equine adipose derived stromal cells.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Hypoxia-Induced Insulin Resistance Mediates the Elevated Cardiovascular Risk in Patients with Obstructive Sleep Apnea: A Comprehensive Review.Reviews in cardiovascular medicine · 2024Review
- Hypoxia-induced PD-L1 expression and modulation of muscle stem cell allograft rejection.Frontiers in pharmacology · 2024Article
- Advances in ex vivo expansion of hematopoietic stem and progenitor cells for clinical applications.Frontiers in bioengineering and biotechnology · 2024Review
- Unraveling the epigenetic landscape of pulmonary arterial hypertension: implications for personalized medicine development.Journal of translational medicine · 2023Review
- SMARCB1 regulates the hypoxic stress response in sickle cell trait.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A glimpse of the connection between PPARγ and macrophage.Frontiers in pharmacology · 2023Review
- Transcription factors in the pathogenesis of pulmonary arterial hypertension-Current knowledge and therapeutic potential.Frontiers in cardiovascular medicine · 2022Review
- Alcohol-Induced Glycolytic Shift in Alveolar Macrophages Is Mediated by Hypoxia-Inducible Factor-1 Alpha.Frontiers in immunology · 2022Article
- Melatonin Attenuates Dasatinib-Aggravated Hypoxic Pulmonary Hypertension via Inhibiting Pulmonary Vascular Remodeling.Frontiers in cardiovascular medicine · 2022Article
- The Influence of Bosentan on MicroRNA-27a/PPARγ/ET-1 Signaling Pathway in Pulmonary Artery Hypertension.Pediatric cardiology · 2021Article
- Exercise retards ongoing adipose tissue fibrosis in diet-induced obese mice.Endocrine connections · 2021Article
- Hypoxia-inducible factor signaling in pulmonary hypertension.The Journal of clinical investigation · 2020Review
- MicroRNA-143-5p modulates pulmonary artery smooth muscle cells functions in hypoxic pulmonary hypertension through targeting HIF-1α.Journal of biosciences · 2020Article
- Focus on Early Events: Pathogenesis of Pulmonary Arterial Hypertension Development.Antioxidants & redox signaling · 2019Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundPathogenesis of pulmonary hypertension is complex and involves activation of the transcription factor, hypoxia-inducible factor-1 (HIF-1) that shifts cellular metabolism from aerobic respiration to glycolysis, in part, by increasing the expression of its downstream target pyruvate dehydrogenase kinase-1 (PDK-1), thereby promoting a proliferative, apoptosis-resistant phenotype in pulmonary vascular cells. Activation of the nuclear hormone transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ), attenuates pulmonary hypertension and pulmonary artery smooth muscle cell (PASMC) proliferation. In the current study, we determined whether PPARγ inhibits HIF-1α and PDK-1 expression in human PASMCs.
methodsHPASMCs were exposed to normoxia (21% O2) or hypoxia (1% O2) for 2-72 hours ± treatment with the PPARγ-ligand, rosiglitazone (RSG, 10μM).
resultsCompared to normoxia, HIF-1α mRNA levels were elevated in HPASMC at 2 hours hypoxia and reduced to baseline levels by 24-72 hours. HIF-1α protein levels increased following 4 and 8 hours of hypoxia and returned to baseline levels by 24 and 72 hours. PDK-1 protein levels increased following 24 hours hypoxia and remained elevated by 72 hours. RSG treatment at the onset of hypoxia attenuated HIF-1α protein and PDK-1 mRNA and protein levels at 4, 8 and 24 hours of hypoxia, respectively. However, RSG treatment during final 24 hours of 72-hour hypoxia, an intervention that inhibits HPASMC proliferation, failed to prevent hypoxia-induced PDK-1 expression.
conclusionHypoxia causes transient activation of HPASMC HIF-1α that is attenuated by RSG treatment initiated at hypoxia onset. These findings provide novel evidence that PPARγ modulates fundamental and acute cellular responses to hypoxia through both HIF-1-dependent and HIF-1-independent mechanisms.
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