ArticlePloS one2022
Hypoxia-induced interstitial transformation of microvascular endothelial cells by mediating HIF-1α/VEGF signaling in systemic sclerosis.
Article in PloS one, 2022. 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, 28 citations in OpenAlex.
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Human MAGI1 expression in endothelial cells protects from the development of localized and systemic scleroderma in mice.Arthritis research & therapy · 2026Article
- Modulation of breast cancer progression in high-altitude hypoxia by Tongqiaohuoxue Decoction via HIF-1α/VEGF signaling.Discover oncology · 2026Article
- Oxytocin supports the barrier integrity of brain endothelial cells via oxytocin receptors.Journal of neuroendocrinology · 2026Article
- Eradication of Small Intestinal Bacterial Overgrowth in Systemic Sclerosis: Current Treatment and Perspectives-A Narrative Review.Biomedicines · 2025Review
- Endothelial-to-mesenchymal transition in the central nervous system: A potential therapeutic target to combat age-related vascular fragility.The Journal of pharmacology and experimental therapeutics · 2025Review
- Identification of LDHA as a Potential Therapeutic Target for Pulmonary Hypertension Through Modulation of Endothelial-To-Mesenchymal Transition.Journal of cellular and molecular medicine · 2025Article
- Molecular Pathogenesis of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Narrative Review.Biomolecules · 2025Review
- Open Microfluidic Cell Culture in Hydrogels Enabled by 3D-Printed Molds.Bioengineering (Basel, Switzerland) · 2025Article
- Common biomarkers of idiopathic pulmonary fibrosis and systemic sclerosis based on WGCNA and machine learning.Scientific reports · 2025Article
- Targeting hypoxia-inducible factor 1α in chronic graft-versus-host disease to enhance graft-versus-leukemia responses: implications for nanotherapeutics.Frontiers in immunology · 2025Review
- The mechanotransduction-immune axis in organ fibrosis: dual regulatory mechanisms and translational therapeutic perspectives.Frontiers in immunology · 2025Review
- Decoding the enigmatic estrogen paradox in pulmonary hypertension: delving into estrogen metabolites and metabolic enzymes.Cellular & molecular biology letters · 2024Review
- Comparative transcriptomic analysis validates iPSC derived in-vitro progressive fibrosis model as a screening tool for drug discovery and development in systemic sclerosis.Scientific reports · 2024Article
- Systemic Sclerosis-Associated Pulmonary Arterial Hypertension: From Bedside to Bench and Back Again.International journal of molecular sciences · 2024Review
- miRNA-146a-5p Inhibits Hypoxia-Induced Myocardial Fibrosis Through EndMT.Cardiovascular toxicology · 2024Article
- Cellular Transdifferentiation: A Crucial Mechanism of Fibrosis in Systemic Sclerosis.Current rheumatology reviews · 2024Review
- Involvement of Epithelial-Mesenchymal Transition (EMT) in Autoimmune Diseases.International journal of molecular sciences · 2023Review
- Hypoxia-Inducible Factor-1α (HIF-1α) as a Biomarker for Changes in Microcirculation in Individuals with Systemic Sclerosis.Dermatology and therapy · 2023Article
- METTL3 Promotes Endothelium-Mesenchymal Transition of Pulmonary Artery Endothelial Cells by Regulating TRPC6/Calcineurin/NFAT Signaling Pathways.Evidence-based complementary and alternative medicine : eCAM · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe aim of this research was to systematically investigate the effects of endothelial mesenchymal transition (EndMT) induced by hypoxia on the skin microvascular remodeling of systemic sclerosis (SSc) and the underlying mechanism.
methodsSkin tissues from SSc patients and controls were collected for isobaric tags for the relative and absolute quantification (iTRAQ)-based proteomics and immunohistochemical test. Human microvascular endothelial cell line-1 (HMEC-1) cultured in hypoxic or normal conditions was treated by tamoxifen or bevacizumab.
resultsThe iTRAQ-based proteomics indicated a significantly upregulated hypoxia-inducible factor-1 (HIF-1) signal in SSc samples. The immunohistochemical results demonstrated the significant downregulation of CD31, the positive staining of α-smooth muscle actin (α-SMA), HIF-1α, and vascular endothelial growth factor (VEGF-a) in SSc skin tissues, compared with control samples. Consistent with these observations, HMEC-1 cells cultured under hypoxic conditions exhibited a significant decrease in CD31 and VE-cadherin expression, alongside a marked increase in the expression of α-SMA and fibronectin, as well as a distinct upregulation of HIF-1α and VEGF-a, when compared with those under normal conditions. It is noteworthy that the inhibition of HIF-1α by tamoxifen effectively downregulated the hypoxic induction of VEGF-a and α-SMA while rescuing the hypoxic suppression of CD31. In addition, the VEGF-a inhibitor bevacizumab treatment had the same effect on the hypoxic expression of α-SMA and CD31, as a tamoxifen intervention, but did not reduce HIF-1α.
conclusionThese results suggest that the HIF-1α/VEGF signaling pathway can have a critical role in mediating the effect of hypoxia-induced EndMT on the skin microvascular remodeling of SSc.
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