ArticleAmerican journal of physiology. Cell physiology2016
PDGF induces SphK1 expression via Egr-1 to promote pulmonary artery smooth muscle cell proliferation.
Article in American journal of physiology. Cell physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Platelet-derived growth factor receptor alpha regulates fetal testis differentiation via an ERK-CREB axis.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Sphingosine kinase 1 is integral for elastin deficiency-induced arterial hypermuscularization.Nature cardiovascular research · 2026Article
- Sphingolipid signaling links elastin deficiency to arterial hyper-muscularization and congenital heart disease.Nature cardiovascular research · 2026Article
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- AFrontiers in cardiovascular medicine · 2024Article
- Sphingosine-1-Phosphate as Lung and Cardiac Vasculature Protecting Agent in SARS-CoV-2 Infection.International journal of molecular sciences · 2023Article
- Deciphering the Mechanism of Wogonin, a Natural Flavonoid, on the Proliferation of Pulmonary Arterial Smooth Muscle Cells by Integrating Network Pharmacology and In Vitro Validation.Current issues in molecular biology · 2023Article
- Sphingosine Kinase 1 Deficiency in Smooth Muscle Cells Protects against Hypoxia-Mediated Pulmonary Hypertension via YAP1 Signaling.International journal of molecular sciences · 2022Article
- Targeting peptidyl-prolyl isomerase 1 in experimental pulmonary arterial hypertension.The European respiratory journal · 2022Article
- PDGF signaling inhibits mitophagy in glioblastoma stem cells through NDevelopmental cell · 2022Article
- Transcription factors in the pathogenesis of pulmonary arterial hypertension-Current knowledge and therapeutic potential.Frontiers in cardiovascular medicine · 2022Review
- Long Noncoding RNACirculation · 2021Article
- My Journey in Academia as a Lipid Biochemist.Cell biochemistry and biophysics · 2021Review
- Programming to S1PR1Circulation research · 2021Article
- Impact of human immunodeficiency virus on pulmonary vascular disease.Global cardiology science & practice · 2021Review
- PDGF mediates pulmonary arterial smooth muscle cell proliferation and migration by regulating NFATc2.Molecular medicine reports · 2021Article
- Oxidative Stress, Kinase Activation, and Inflammatory Pathways Involved in Effects on Smooth Muscle Cells During Pulmonary Artery Hypertension Under Hypobaric Hypoxia Exposure.Frontiers in physiology · 2021Review
- Mechanistic regulation of SPHK1 expression and translocation by EMAP II in pulmonary smooth muscle cells.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Article
- Effect of Sphingosine-1-Phosphate on Intracellular Free Ca²⁺ in Cat Esophageal Smooth Muscle Cells.Biomolecules & therapeutics · 2018Article
- Inhibitory Antibodies against Activin A and TGF-β Reduce Self-Supported, but Not Soluble Factors-Induced Growth of Human Pulmonary Arterial Vascular Smooth Muscle Cells in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2018Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Pulmonary arterial hypertension (PAH) is a progressive, life-threatening disease for which there is currently no curative treatment available. Pathologic changes in this disease involve remodeling of the pulmonary vasculature, including marked proliferation of pulmonary artery smooth muscle cells (PASMCs). Recently, the bioactive lipid sphingosine-1-phosphate (S1P) and its activating kinase, sphingosine kinase 1 (SphK1), have been shown to be upregulated in PAH and promote PASMC proliferation. The mechanisms regulating the transcriptional upregulation of SphK1 in PASMCs are unknown. In this study, we investigated the role of platelet-derived growth factor (PDGF), a PAH-relevant stimuli associated with enhanced PASMC proliferation, on SphK1 expression regulation. In human PASMCs (hPASMCs), PDGF significantly increased SphK1 mRNA and protein expression and induced cell proliferation. Selective inhibition of SphK1 attenuated PDGF-induced hPASMC proliferation. In silico promoter analysis for SphK1 identified several binding sites for early growth response protein 1 (Egr-1), a PDGF-associated transcription factor. Luciferase assays demonstrated that PDGF activates the SphK1 promoter in hPASMCs, and truncation of the 5'-promoter reduced PDGF-induced SphK1 expression. Stimulation of hPASMCs with PDGF induced Egr-1 protein expression, and direct binding of Egr-1 to the SphK1 promoter was confirmed by chromatin immunoprecipitation analysis. Inhibition of ERK signaling prevented induction of Egr-1 by PDGF. Silencing of Egr-1 attenuated PDGF-induced SphK1 expression and hPASMC proliferation. These studies demonstrate that SphK1 is regulated by PDGF in hPASMCs via the transcription factor Egr-1, promoting cell proliferation. This novel mechanism of SphK1 regulation may be a therapeutic target in pulmonary vascular remodeling 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.