ArticlePulmonary pharmacology & therapeutics2019
SUMOylation of Vps34 by SUMO1 promotes phenotypic switching of vascular smooth muscle cells by activating autophagy in pulmonary arterial hypertension.
Article in Pulmonary pharmacology & therapeutics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Histone modification of endothelial-mesenchymal transition in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Pooled it
- Identification of Key Genes Related to SUMOylation and Potassium Channels and Their Mechanism of Influence on Pulmonary Arterial Hypertension.Biochemical genetics · 2026Article
- Post-translational modification crosstalk in pulmonary arterial hypertension: mechanisms and therapeutic implications.Molecular biology reports · 2026Review
- Fisetin alleviates pulmonary arterial hypertension by inhibiting the TGF-β1/Smad 2/3 signaling pathway.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Article
- Class III Phosphatidylinositol-3 Kinase/Vacuolar Protein Sorting 34 in Cardiovascular Health and Disease.Journal of cardiovascular translational research · 2025Review
- Review
- Mechanistic Insights into the Therapeutic Efficacy of Qi Ling Gui Fu Prescription in Broiler Ascites Syndrome: A Network Pharmacology and Experimental Study.Veterinary sciences · 2025Article
- Irisin suppresses PDGF-BB-induced proliferation of vascular smooth muscle cellsEuropean journal of histochemistry : EJH · 2024Article
- DNA methylation in peripheral blood is associated with renal aging and renal function decline: a national community study.Clinical epigenetics · 2024Article
- Metabolic pathways, genomic alterations, and post-translational modifications in pulmonary hypertension and cancer as therapeutic targets and biomarkers.Frontiers in pharmacology · 2024Article
- The emerging roles of SUMOylation in pulmonary diseases.Molecular medicine (Cambridge, Mass.) · 2023Review
- Proteomics Studies Suggest That Nitric Oxide Donor Furoxans Inhibit In Vitro Vascular Smooth Muscle Cell Proliferation by Nitric Oxide-Independent Mechanisms.Molecules (Basel, Switzerland) · 2023Article
- The role of SUMOylation in the neurovascular dysfunction after acquired brain injury.Frontiers in pharmacology · 2023Review
- Research progress on the mechanism of phenotypic transformation of pulmonary artery smooth muscle cells induced by hypoxia.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2022Review
- SUMOylation targeting mitophagy in cardiovascular diseases.Journal of molecular medicine (Berlin, Germany) · 2022Review
- Deletion of SUMO1 attenuates behavioral and anatomical deficits by regulating autophagic activities in Huntington disease.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The role of post-translational modifications in driving abnormal cardiovascular complications at high altitude.Frontiers in cardiovascular medicine · 2022Review
- SUMO1 Promotes Mesangial Cell Proliferation Through Inhibiting Autophagy in a Cell Model of IgA Nephropathy.Frontiers in medicine · 2022Article
- Class III phosphatidylinositol 3-kinase complex I subunit NRBF2/Atg38 - from cell and structural biology to health and disease.Autophagy · 2021Review
- The Role of Phosphatidylinositol 3-Kinase Catalytic Subunit Type 3 in the Pathogenesis of Human Cancer.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
introductionPulmonary arterial hypertension (PAH) is a life-threatening disease without effective therapies. PAH is associated with a progressive increase in pulmonary vascular resistance and irreversible pulmonary vascular remodeling. SUMO1 (small ubiquitin-related modifier 1) can bind to target proteins and lead to protein SUMOylation, an important post-translational modification with a key role in many diseases. However, the contribution of SUMO1 to PAH remains to be fully characterized.
methodsIn this study, we explored the role of SUMO1 in the dedifferentiation of vascular smooth muscle cells (VSMCs) involved in hypoxia-induced pulmonary vascular remodeling and PAH in vivo and in vitro.
resultsIn a mouse model of hypoxic PAH, SUMO1 expression was significantly increased, which was associated with activation of autophagy (increased LC3b and decreased p62), dedifferentiation of pulmonary arterial VSMCs (reduced α-SMA, SM22 and SM-MHC), and pulmonary vascular remodeling. Similar results were obtained in a MCT-induced PAH model. Overexpression of SUMO1 significantly increased VSMCs proliferation, migration, hypoxia-induced VSMCs dedifferentiation, and autophagy, but these effects were abolished by inhibition of autophagy by 3-MA in aortic VSMCs. Furthermore, SUMO1 knockdown reversed hypoxia-induced proliferation and migration of PASMCs. Mechanistically, SUMO1 promotes Vps34 SUMOylation and the assembly of the Beclin-1-Vps34-Atg14 complex, thereby inducing autophagy, whereas Vps34 mutation K840R reduces Vps34 SUMOylation and inhibits VSMCs dedifferentiation. DISCUSSION: Our data uncovers an important role of SUMO1 in VSMCs proliferation, migration, autophagy, and phenotypic switching (dedifferentiation) involved in pulmonary vascular remodeling and PAH. Targeting of the SUMO1-Vps34-autophagy signaling axis may be exploited to develop therapeutic strategies to treat PAH.
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Registered trials
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.