ArticleThe Journal of biological chemistry2014
Peroxisome proliferator-activated receptor-α-mediated transcription of miR-199a2 attenuates endothelin-1 expression via hypoxia-inducible factor-1α.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- MiR-199a-3p deficiency induced by STAT3 activation drives smooth muscle cell phenotypic switching in pulmonary arterial hypertension.Non-coding RNA research · 2026Article
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- High-Dose Fenofibrate Stimulates Multiple Cellular Stress Pathways in the Kidney of Old Rats.International journal of molecular sciences · 2024Article
- Long Non-coding RNA DNM3OS: Pathogenic Roles and Molecular Mechanisms in Pathophysiological Processes.Current medicinal chemistry · 2024Review
- The Emerging Therapeutic Role of Prostaglandin E2 Signaling in Pulmonary Hypertension.Metabolites · 2023Review
- The inflammatory profiles of pulmonary alveolar macrophages and alveolar type 2 cells in SCD.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Hypoxia-inducible factor signaling in pulmonary hypertension.The Journal of clinical investigation · 2020Review
- The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease.Frontiers in immunology · 2020Review
- Micromanaging aerobic respiration and glycolysis in cancer cells.Molecular metabolism · 2019Review
- Recent research progress of microRNAs in hypertension pathogenesis, with a focus on the roles of miRNAs in pulmonary arterial hypertension.Molecular biology reports · 2018Review
- Diabetes Mellitus-Induced Long Noncoding RNA Dnm3os Regulates Macrophage Functions and Inflammation via Nuclear Mechanisms.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Protein Z and Endothelin-1 genetic polymorphisms in pediatric Egyptian sickle cell disease patients.Journal of clinical laboratory analysis · 2018Article
- Placenta growth factor mediated gene regulation in sickle cell disease.Blood reviews · 2018Review
- PPARBioMed research international · 2018Article
- A functional variant in ST2 gene is associated with risk of hypertension via interfering MiR-202-3p.Journal of cellular and molecular medicine · 2017Article
- Review
- Comparative analysis of the mechanical signals in lung development and compensatory growth.Cell and tissue research · 2017Review
- Peroxisome Proliferator-Activated Receptor γ Regulates the V-Ets Avian Erythroblastosis Virus E26 Oncogene Homolog 1/microRNA-27a Axis to Reduce Endothelin-1 and Endothelial Dysfunction in the Sickle Cell Mouse Lung.American journal of respiratory cell and molecular biology · 2017Article
- Polymorphism of the endothelin-1 gene (rs5370) is a potential contributor to sickle cell disease pathophysiology.Genes & diseases · 2016Article
- Activated Transcription Factor 3 in Association with Histone Deacetylase 6 Negatively Regulates MicroRNA 199a2 Transcription by Chromatin Remodeling and Reduces Endothelin-1 Expression.Molecular and cellular biology · 2016Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Endothelin-1, a potent vasoconstrictor, plays an important role in pulmonary hypertension (PH) in sickle cell disease (SCD). Our previous studies show that higher levels of placenta growth factor (PlGF), secreted by erythroid precursor cells, correlate with increased plasma levels of endothelin-1 (ET-1) and other functional markers of PH in SCD. PlGF-mediated ET-1 expression occurs via activation of hypoxia-inducible factor-1α (HIF-1α). However, relatively less is understood regarding how PlGF-mediated expression of HIF-1α and its downstream effector ET-1 are post-transcriptionally regulated. Herein, we show that PlGF treatment of endothelial cells resulted in reduced levels of miR-199a2, which targeted the 3'-UTR of HIF-1α mRNA and concomitantly led to augmented ET-1 expression. Plasma levels of miR-199a2 in SCD subjects were significantly lower with reciprocally high levels of plasma ET-1, unlike unaffected controls. This observation provided a molecular link between miR-199a2 and high levels of ET-1 in SCD. Furthermore, we show that miR-199a2 located in the DNM3os transcription unit was co-transcriptionally regulated by peroxisome proliferator-activated receptor α (PPARα). Binding of the latter to PPARα cis-elements in the promoter of DNM3os was demonstrated by promoter mutational analysis and ChIP. Additionally, we show that fenofibrate, a PPARα agonist, increased the expression of miR-199a2 and DNM3os; the former was responsible for reduced expression of HIF-1α and ET-1. In vivo studies of fenofibrate-fed Berkeley sickle mice resulted in increased levels of miR-199a2 and reduced levels of ET-1 in lung tissues. Our studies provide a potential therapeutic approach whereby fenofibrate-induced miR-199a2 expression can ameliorate PH by reduction of ET-1 levels.
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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 OpenQuestion graph.