ArticleToxins2021
Indoxyl Sulfate Contributes to mTORC1-Induced Renal Fibrosis via The OAT/NADPH Oxidase/ROS Pathway.
Article in Toxins, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
36 citing papers in PubMed, 51 citations in OpenAlex.
- Gut Microbiota and Their Metabolites in Acute Kidney Injury: Classification, Mechanisms, and Therapeutic Potential.Metabolites · 2026Review
- Acute Kidney Injury-to-Chronic Kidney Disease Transition-Associated Macrophage Subtypes: Biological Functions and Intercellular Crosstalk.International journal of molecular sciences · 2026Review
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Review
- Purine-Metabolism Reprogramming Associated with Failed-Repair Proximal Tubule States in the AKI-to-CKD Transition.Metabolites · 2026Article
- Evaluation of the effect of Renaltec in cats with IRIS stage 2 and 3 chronic kidney disease.Journal of feline medicine and surgery · 2026Article
- Bridging gut microbiota and renal health: Klotho as a promising therapeutic agent in DKD.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Gut dysbiosis and constipation in patients with end-stage renal disease: pathogenic associations and therapeutic interventions.Frontiers in cellular and infection microbiology · 2026Review
- Indoxyl sulfate in the gut-kidney axis: from diet-microbiome interactions to renal injury and targeted therapies.Frontiers in nutrition · 2026Review
- The effect of pre-transplant dialysis duration on the relationship between delayed graft function and recipient death.Scientific reports · 2025Article
- Klotho Suppresses Indoxyl Sulfate-Mediated Apoptosis in Human Kidney Proximal Tubular (HK-2) Cells through Modulating the AKT/Nrf2 Mechanism.ACS omega · 2025Article
- Gut Microbiota and Their Metabolites: The Hidden Driver of Diabetic Nephropathy? Unveiling Gut Microbe's Role in DN.Journal of diabetes · 2025Review
- Structural basis for cholesterol sensing of LYCHOS and its interaction with indoxyl sulfate.Nature communications · 2025Article
- Combating chronic kidney disease-associated cachexia: A literature review of recent therapeutic approaches.BMC nephrology · 2025Review
- Identification of potential biomarkers for diabetic nephropathy via UPLC-MS/MS-based metabolomics.Frontiers in endocrinology · 2025Article
- Unraveling the mysteries of the gut-kidney axis: the protective role of traditional Chinese medicine in chronic kidney disease.Frontiers in microbiology · 2025Review
- The evaluation of indoxyl sulfate in the general population in Kanegasaki Iwate: A cross-sectional study (KANEGASAKI study).PloS one · 2025Observational
- TXNIP deficiency attenuates renal fibrosis by modulating mTORC1/TFEB-mediated autophagy in diabetic kidney disease.Renal failure · 2024Article
- Renal anemia: from relative insufficiency of EPO to imbalance of erythropoiesis and eryptosis.International urology and nephrology · 2024Review
- In laying hens, chronic heat stress-induced renal fibrosis is potentially promoted by indoxyl sulfate.Scientific reports · 2024Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of mTORC1 (mechanistic target of rapamycin complex 1) in renal tissue has been reported in chronic kidney disease (CKD)-induced renal fibrosis. However, the molecular mechanisms responsible for activating mTORC1 in CKD pathology are not well understood. The purpose of this study was to identify the uremic toxin involved in mTORC1-induced renal fibrosis. Among the seven protein-bound uremic toxins, only indoxyl sulfate (IS) caused significant activation of mTORC1 in human kidney 2 cells (HK-2 cells). This IS-induced mTORC1 activation was inhibited in the presence of an organic anion transporter inhibitor, a NADPH oxidase inhibitor, and an antioxidant. IS also induced epithelial-mesenchymal transition of tubular epithelial cells (HK-2 cells), differentiation of fibroblasts into myofibroblasts (NRK-49F cells), and inflammatory response of macrophages (THP-1 cells), which are associated with renal fibrosis, and these effects were inhibited in the presence of rapamycin (mTORC1 inhibitor). In in vivo experiments, IS overload was found to activate mTORC1 in the mouse kidney. The administration of AST-120 or rapamycin targeted to IS or mTORC1 ameliorated renal fibrosis in Adenine-induced CKD mice. The findings reported herein indicate that IS activates mTORC1, which then contributes to renal fibrosis. Therapeutic interventions targeting IS and mTORC1 could be effective against renal fibrosis in CKD.
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