ArticlePloS one2016
Endothelium-Derived 5-Methoxytryptophan Protects Endothelial Barrier Function by Blocking p38 MAPK Activation.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 40 citations in OpenAlex.
- Whole-Genome Sequence Analysis and Probiotic Characterization of 5-Methoxytryptophan-Producing StrainMicroorganisms · 2026Article
- The effect of 5MTP on the expression of inflammatory markers in human aortic endothelial cell.Acta diabetologica · 2026Article
- iPSC-Derived Endothelial Cells as Experimental Models for Predictive and Personalized Strategies in Cardiovascular and Cerebrovascular Disease.International journal of molecular sciences · 2026Review
- NMN protects vascular endothelial cells from M1 macrophage-derived IL-1β-induced hyperpermeability by inhibiting VE-cadherin degradation.Frontiers in cardiovascular medicine · 2026Article
- Smooth muscle-specific expression of hydroxyindole O-methyltransferase reduces arterial injury-induced intimal hyperplasia.Journal of biomedical science · 2025Article
- Control of inflammatory lung injury and repair by metabolic signaling in endothelial cells.Current opinion in hematology · 2025Review
- 5-Methoxytryptophan Protects against Toll-Like Receptor 2-Mediated Renal Tissue Inflammation and Fibrosis in a Murine Unilateral Ureteral Obstruction Model.Journal of innate immunity · 2025Article
- Tryptophan metabolism as a target in gut microbiota, ageing and kidney disease.International journal of biological sciences · 2025Review
- Microenvironmental acidification by pneumococcal sugar consumption fosters barrier disruption and immune suppression in the human alveolus.The European respiratory journal · 2024Article
- 5-Methoxytryptophan enhances the sensitivity of sorafenib on the inhibition of proliferation and metastasis for lung cancer cells.BMC cancer · 2024Article
- 5-Methoxytryptophan Alleviates Dextran Sulfate Sodium-Induced Colitis by Inhibiting the Intestinal Epithelial Damage and Inflammatory Response.Mediators of inflammation · 2024Article
- 5-methoxytryptophan induced apoptosis and PI3K/Akt/FoxO3a phosphorylation in colorectal cancer.World journal of gastroenterology · 2023Article
- Characterizing the metabolic response of the zebrafish kidney to overfeeding.American journal of physiology. Renal physiology · 2023Article
- Article
- 5-Methoxytryptophan Sensitizing Head and Neck Squamous Carcinoma Cell to Cisplatitn Through Inhibiting Signal Transducer and Activator of Transcription 3 (STAT3).Frontiers in oncology · 2022Article
- Restoration of 5-methoxytryptophan protects against atherosclerotic chondrogenesis and calcification in ApoEJournal of biomedical science · 2021Article
- Cytoguardin: A Tryptophan Metabolite against Cancer Growth and Metastasis.International journal of molecular sciences · 2021Review
- Control of Mesenchymal Stromal Cell Senescence by Tryptophan Metabolites.International journal of molecular sciences · 2021Review
- Control of Tissue Fibrosis by 5-Methoxytryptophan, an Innate Anti-Inflammatory Metabolite.Frontiers in pharmacology · 2021Review
- 5-methoxytryptophan: an arsenal against vascular injury and inflammation.Journal of biomedical science · 2020Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endothelial junction is tightly controlled to restrict the passage of blood cells and solutes. Disruption of endothelial barrier function by bacterial endotoxins, cytokines or growth factors results in inflammation and vascular damage leading to vascular diseases. We have identified 5-methoxytryptophan (5-MTP) as an anti-inflammatory factor by metabolomic analysis of conditioned medium of human fibroblasts. Here we postulated that endothelial cells release 5-MTP to protect the barrier function. Conditioned medium of human umbilical vein endothelial cells (HUVECs) prevented endothelial hyperpermeability and VE-cadherin downregulation induced by VEGF, LPS and cytokines. We analyzed the metabolomic profile of HUVEC conditioned medium and detected 5-MTP but not melatonin, serotonin or their catabolites, which was confirmed by enzyme-linked immunosorbent assay. Addition of synthetic pure 5-MTP preserved VE-cadherin and maintained barrier function despite challenge with pro-inflammatory mediators. Tryptophan hydroxylase-1, an enzyme required for 5-MTP biosynthesis, was downregulated in HUVECs by pro-inflammatory mediators and it was accompanied by reduction of 5-MTP. 5-MTP protected VE-cadherin and prevented endothelial hyperpermeability by blocking p38 MAPK activation. A chemical inhibitor of p38 MAPK, SB202190, exhibited a similar protective effect as 5-MTP. To determine whether 5-MTP prevents vascular hyperpermeability in vivo, we evaluated the effect of 5-MTP administration on LPS-induced murine microvascular permeability with Evans blue. 5-MTP significantly prevented Evans blue dye leakage. Our findings indicate that 5-MTP is a new class of endothelium-derived molecules which protects endothelial barrier function by blocking p38 MAPK.
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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.