ArticleThe Journal of clinical investigation2022
Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.
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Who cites it
48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 61 citations in OpenAlex.
- Metabolomics biomarkers and related pathways in acute renal injury: a bibliometric investigation, meta-analysis, and systematic review.Frontiers in medicine · 2025Pooled it
- Indoxyl Sulfate and Autism Spectrum Disorder: A Literature Review.International journal of molecular sciences · 2024Pooled it
- Stenosis in Mature Arteriovenous Fistulas Characterized by Contractile Smooth Muscle Cells and Versican.Kidney international reports · 2026Article
- Uremic toxins promote renal fatty acid synthesis and fibrosis via activating aryl hydrocarbon receptor.Nature communications · 2026Article
- Impact of kidney dysfunction on outcomes in peripheral artery disease: A multi-database cohort study.iScience · 2026Article
- Sexual dimorphism shapes renal metabolic adaptation to a ketogenic diet.Cell reports · 2026Article
- Tryptophan metabolism reprogramming potentially contributes to the prothrombotic milieu in mice and humans with SARS-CoV-2.Blood vessels, thrombosis & hemostasis · 2026Article
- A Murine Model of Cardiovascular-Kidney-Metabolic Syndrome Demonstrates Compromised Limb Function in the Ischemic Hind Limb.Kidney360 · 2026Article
- Rapid LC-MS/MS-based quantitative serum tryptophan metabolomics platform identifies and monitors novel biomarkers for diabetic kidney disease.Analytical and bioanalytical chemistry · 2026Article
- A guide to uraemic toxicity.Nature reviews. Nephrology · 2026Review
- Gut microbial-derived metabolites: key players in kidney disease and renal fibrosis.International journal of biological sciences · 2026Review
- Epicardial adipose tissue: an overtly concealed contributor to cardiovascular events in chronic kidney disease patients.Lipids in health and disease · 2025Review
- Pirfenidone treatment improves ischemic muscle function in mice with chronic kidney disease.Skeletal muscle · 2025Article
- Dietary tryptophan augments cancer-associated venous thrombogenicity mitigated by indoleamine 2,3-dioxygenase 1 inhibition.Blood advances · 2025Article
- Interleukin-10 deficiency suppresses colorectal cancer metastasis by enriching gut Parabacteroides distasonis.Journal of advanced research · 2025Article
- The microbiome in cancer.iMeta · 2025Review
- Article
- The Non-Traditional Cardiovascular Culprits in Chronic Kidney Disease: Mineral Imbalance and Uremic Toxin Accumulation.International journal of molecular sciences · 2025Review
- Clinical management of peripheral arterial disease in chronic kidney disease-a comprehensive review from the European Renal Association CKD-MBD Working Group.Clinical kidney journal · 2025Review
- Activation and targetability of TYMP-IL-6-TF signaling in the skin microenvironment in uremic calciphylaxis.Science translational medicine · 2025Article
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19 authors at 5 institutions in 2 countries.
Funding
Abstract
Chronic kidney disease (CKD) imposes a strong and independent risk for peripheral artery disease (PAD). While solutes retained in CKD patients (uremic solutes) inflict vascular damage, their role in PAD remains elusive. Here, we show that the dietary tryptophan-derived uremic solutes including indoxyl sulfate (IS) and kynurenine (Kyn) at concentrations corresponding to those in CKD patients suppress β-catenin in several cell types, including microvascular endothelial cells (ECs), inhibiting Wnt activity and proangiogenic Wnt targets in ECs. Mechanistic probing revealed that these uremic solutes downregulated β-catenin in a manner dependent on serine 33 in its degron motif and through the aryl hydrocarbon receptor (AHR). Hindlimb ischemia in adenine-induced CKD and IS solute-specific mouse models showed diminished β-catenin and VEGF-A in the capillaries and reduced capillary density, which correlated inversely with blood levels of IS and Kyn and AHR activity in ECs. An AHR inhibitor treatment normalized postischemic angiogenic response in CKD mice to a non-CKD level. In a prospective cohort of PAD patients, plasma levels of tryptophan metabolites and plasma's AHR-inducing activity in ECs significantly increased the risk of future adverse limb events. This work uncovers the tryptophan metabolite/AHR/β-catenin axis as a mediator of microvascular rarefaction in CKD patients and demonstrates its targetability for PAD in CKD models.
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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.