ArticleHypertension (Dallas, Tex. : 1979)2023
E2F1 Mediates SOX17 Deficiency-Induced Pulmonary Hypertension.
Article in Hypertension (Dallas, Tex. : 1979), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 17 citations in OpenAlex.
- Secretory Carrier Membrane Protein 3 Knockdown Attenuates Hypoxic Pulmonary Hypertension Potentially Involving WW Domain-Containing E3 Ubiquitin Protein Ligase 1.Biochemical genetics · 2026Article
- E2F1 Drives Endothelial Arterial Programming in Pulmonary Arterial Hypertension.bioRxiv : the preprint server for biology · 2026Article
- Identification of drug candidates for rescue of SOX17 gene targets in pulmonary arterial hypertension.bioRxiv : the preprint server for biology · 2026Article
- Experimental pulmonary arterial hypertension in mice with a pathogenic SOX17 variant.Scientific reports · 2026Article
- Advances in the pathogenesis and clinical management of pulmonary hypertension.Medical review (2021) · 2026Review
- IL-33 Drives Endothelial-to-Mesenchymal Transition in Pulmonary Hypertension.Hypertension (Dallas, Tex. : 1979) · 2026Article
- SOX17-silenced HPAECs upregulate NF-κB-induced CXCL10 and CXCL11: implications for lymphocyte chemotaxis in SOX17-PAH.Scientific reports · 2025Article
- SOX17 in pulmonary arterial hypertension: from development to clinical phenotype.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Unraveling the SOX11-IGF2 signaling axis in early lung development: implications for lung disease.Communications biology · 2025Article
- The prognostic and neuroendocrine implications of SLC25A29-mediated biomass signature in prostate cancer.GeroScience · 2025Article
- Guarding the Endothelium: SOX17's Crucial Role in Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2025Article
- Review
- The role of E2F1 in promoting EIF4EBP1 transcription in cryptorchid mice: association with autophagy in germ cells.Frontiers in genetics · 2025Article
- Article
- A Novel Animal Model for Pulmonary Hypertension: Lung Endothelial-Specific Deletion ofJournal of respiratory biology and translational medicine · 2024Article
- Light at the ENDothelium-role of Sox17 and Runx1 in endothelial dysfunction and pulmonary arterial hypertension.Frontiers in cardiovascular medicine · 2023Review
- Endothelial cell clonality, heterogeneity and dysfunction in pulmonary arterial hypertension.Frontiers in medicine · 2023Review
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18 authors at 6 institutions in 3 countries.
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Abstract
backgroundRare genetic variants and genetic variation at loci in an enhancer in SOX17 (SRY-box transcription factor 17) are identified in patients with idiopathic pulmonary arterial hypertension (PAH) and PAH with congenital heart disease. However, the exact role of genetic variants or mutations in SOX17 in PAH pathogenesis has not been reported.
methodsSOX17 expression was evaluated in the lungs and pulmonary endothelial cells (ECs) of patients with idiopathic PAH. Mice with Tie2Cre-mediated Sox17 knockdown and EC-specific Sox17 deletion were generated to determine the role of SOX17 deficiency in the pathogenesis of PAH. Human pulmonary ECs were cultured to understand the role of SOX17 deficiency. Single-cell RNA sequencing, RNA-sequencing analysis, and luciferase assay were performed to understand the underlying molecular mechanisms of SOX17 deficiency-induced PAH. E2F1 (E2F transcription factor 1) inhibitor HLM006474 was used in EC-specific Sox17 mice.
resultsSOX17 expression was downregulated in the lung and pulmonary ECs from patients with idiopathic PAH. Mice with Tie2Cre-mediated Sox17 knockdown and EC-specific Sox17 deletion induced spontaneously mild pulmonary hypertension. Loss of endothelial Sox17 in EC exacerbated hypoxia-induced pulmonary hypertension in mice. Loss of SOX17 in lung ECs induced endothelial dysfunctions including upregulation of cell cycle programming, proliferative and antiapoptotic phenotypes, augmentation of paracrine effect on pulmonary arterial smooth muscle cells, impaired cellular junction, and BMP (bone morphogenetic protein) signaling. E2F1 signaling was shown to mediate the SOX17 deficiency-induced EC dysfunction. Pharmacological inhibition of E2F1 in Sox17 EC-deficient mice attenuated pulmonary hypertension development.
conclusionsOur study demonstrated that endothelial SOX17 deficiency induces pulmonary hypertension through E2F1. Thus, targeting E2F1 signaling represents a promising approach in patients with PAH.
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