ArticleProceedings of the National Academy of Sciences of the United States of America2013
S-nitrosoglutathione reductase (GSNOR) enhances vasculogenesis by mesenchymal stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- The impact of cell-based therapy on female sexual dysfunction: a systematic review and meta-analysis.Sexual medicine reviews · 2023Pooled it
- Does transendocardial injection of mesenchymal stem cells improve myocardial function locally or globally?: An analysis from the Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis (POSEIDON) randomized trial.Circulation research · 2014Trial
- S-nitrosoglutathione reductase GSNOR drives age-related obesity by promoting adipose tissue whitening through de-nitrosation of Beclin-1.Nature communications · 2026Article
- Growth hormone-releasing hormone signaling and manifestations within the cardiovascular system.Reviews in endocrine & metabolic disorders · 2025Review
- Effects of GHRH and its analogues on the Vascular System.Reviews in endocrine & metabolic disorders · 2025Review
- Growth hormone-releasing hormone and its analogues in health and disease.Nature reviews. Endocrinology · 2025Review
- S-Nitrosylation of NOTCH1 Regulates Mesenchymal Stem Cells Differentiation Into Hepatocyte-Like Cells by Inhibiting Notch Signalling Pathway.Journal of cellular and molecular medicine · 2024Article
- Mitochondrial destabilization in tendinopathy and potential therapeutic strategies.Journal of orthopaedic translation · 2024Review
- Translational potential of mesenchymal stem cells in regenerative therapies for human diseases: challenges and opportunities.Stem cell research & therapy · 2024Review
- Unveiling the role of KSHV-infected human mesenchymal stem cells in Kaposi's sarcoma initiation.Journal of medical virology · 2024Article
- S-nitrosylation attenuates pregnane X receptor hyperactivity and acetaminophen-induced liver injury.JCI insight · 2024Article
- Transforming Perspectives in Cardiac Cell Therapy: Hypothesis and Commentary Following Updated Results of a Pilot Study Investigating Very Long-Term Clinical Outcomes in Severe AMI Patients Following Trans-Epicardial Injection of Peripheral Blood CD34Stem cell reviews and reports · 2024Article
- Review
- State of the field: cellular and exosomal therapeutic approaches in vascular regeneration.American journal of physiology. Heart and circulatory physiology · 2022Review
- S-Nitrosoglutathione Reductase Deficiency Causes Aberrant Placental S-Nitrosylation and Preeclampsia.Journal of the American Heart Association · 2022Article
- Kaposi's sarcoma herpesvirus activates the hypoxia response to usurp HIF2α-dependent translation initiation for replication and oncogenesis.Cell reports · 2021Article
- Protein S-nitrosylation regulates proteostasis and viability of hematopoietic stem cell during regeneration.Cell reports · 2021Article
- Cardiac Derived CD51-Positive Mesenchymal Stem Cells Enhance the Cardiac Repair Through SCF-Mediated Angiogenesis in Mice With Myocardial Infarction.Frontiers in cell and developmental biology · 2021Article
- Functions of Mesenchymal Stem Cells in Cardiac Repair.Advances in experimental medicine and biology · 2021Article
- Rejuvenation of Senescent Endothelial Progenitor Cells by Extracellular Vesicles Derived From Mesenchymal Stromal Cells.JACC. Basic to translational science · 2020Article
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10 authors at 3 institutions in 2 countries.
Funding
Abstract
Although nitric oxide (NO) signaling promotes differentiation and maturation of endothelial progenitor cells, its role in the differentiation of mesenchymal stem cells (MSCs) into endothelial cells remains controversial. We tested the role of NO signaling in MSCs derived from WT mice and mice homozygous for a deletion of S-nitrosoglutathione reductase (GSNOR(-/-)), a denitrosylase that regulates S-nitrosylation. GSNOR(-/-) MSCs exhibited markedly diminished capacity for vasculogenesis in an in vitro Matrigel tube-forming assay and in vivo relative to WT MSCs. This decrease was associated with down-regulation of the PDGF receptorα (PDGFRα) in GSNOR(-/-) MSCs, a receptor essential for VEGF-A action in MSCs. Pharmacologic inhibition of NO synthase with L-N(G)-nitroarginine methyl ester (L-NAME) and stimulation of growth hormone-releasing hormone receptor (GHRHR) with GHRH agonists augmented VEGF-A production and normalized tube formation in GSNOR(-/-) MSCs, whereas NO donors or PDGFR antagonist reduced tube formation ∼50% by murine and human MSCs. The antagonist also blocked the rescue of tube formation in GSNOR(-/-) MSCs by L-NAME or the GHRH agonists JI-38, MR-409, and MR-356. Therefore, GSNOR(-/-) MSCs have a deficient capacity for endothelial differentiation due to downregulation of PDGFRα related to NO/GSNOR imbalance. These findings unravel important aspects of modulation of MSCs by VEGF-A activation of the PDGFR and illustrate a paradoxical inhibitory role of S-nitrosylation signaling in MSC vasculogenesis. Accordingly, disease states characterized by NO deficiency may trigger MSC-mediated vasculogenesis. These findings have important implications for therapeutic application of GHRH agonists to ischemic disorders.
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