ArticleThe Journal of biological chemistry2017
A dual agonist of farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5, INT-767, reverses age-related kidney disease in mice.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 67 citations in OpenAlex.
- Bile acid signaling, metabolism, and aging.Liver research (Beijing, China) · 2026Review
- RPL5 deficiency-induced ribosomal stress targets a select subset of proteins and inhibits the PI3K-Akt-mTOR signaling pathway to eradicate leukemia stem cells.Cell death & disease · 2025Article
- Role of nuclear receptors, lipid metabolism, and mitochondrial function in the pathogenesis of diabetic kidney disease.American journal of physiology. Renal physiology · 2025Review
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- Lipid Accumulation and Insulin Resistance: Bridging Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Kidney Disease.International journal of molecular sciences · 2025Review
- Crosstalk Between Bile Acids and Intestinal Epithelium: Multidimensional Roles of Farnesoid X Receptor and Takeda G Protein Receptor 5.International journal of molecular sciences · 2025Review
- Targeting farnesoid X receptor as aging intervention therapy.Acta pharmaceutica Sinica. B · 2025Article
- Takeda G protein-coupled receptor 5 (TGR5): an attractive therapeutic target for aging-related cardiovascular diseases.Frontiers in pharmacology · 2025Review
- Role of Bile Acid Receptors in the Development and Function of Diabetic Nephropathy.Kidney international reports · 2024Review
- Transporter Proteins as Therapeutic Drug Targets-With a Focus on SGLT2 Inhibitors.International journal of molecular sciences · 2024Review
- Circulating concentrations of bile acids and prevalent chronic kidney disease among newly diagnosed type 2 diabetes: a cross-sectional study.Nutrition journal · 2024Article
- Gut microbiota and bile acids: Metabolic interactions and impacts on diabetic kidney disease.Current research in microbial sciences · 2024Review
- Estrogen-Related Receptor Agonism Reverses Mitochondrial Dysfunction and Inflammation in the Aging Kidney.The American journal of pathology · 2023Article
- Article
- Peroxisome proliferator-activated receptors, farnesoid X receptor, and dual modulating drugs in hypertension.Frontiers in physiology · 2023Review
- Bile acid receptors and renal regulation of water homeostasis.Frontiers in physiology · 2023Review
- Dual soluble epoxide hydrolase inhibitor - farnesoid X receptor agonist interventional treatment attenuates renal inflammation and fibrosis.Frontiers in immunology · 2023Article
- High-Amylose Corn Starch Regulated Gut Microbiota and Serum Bile Acids in High-Fat Diet-Induced Obese Mice.International journal of molecular sciences · 2022Article
- Association of metabolic dysfunction-associated fatty liver disease with kidney disease.Nature reviews. Nephrology · 2022Review
- Bile acids and salt-sensitive hypertension: a role of the gut-liver axis.American journal of physiology. Heart and circulatory physiology · 2022Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Even in healthy individuals, renal function gradually declines during aging. However, an observed variation in the rate of this decline has raised the possibility of slowing or delaying age-related kidney disease. One of the most successful interventional measures that slows down and delays age-related kidney disease is caloric restriction. We undertook the present studies to search for potential factors that are regulated by caloric restriction and act as caloric restriction mimetics. Based on our prior studies with the bile acid-activated nuclear hormone receptor farnesoid X receptor (FXR) and G protein-coupled membrane receptor TGR5 that demonstrated beneficial effects of FXR and TGR5 activation in the kidney, we reasoned that FXR and TGR5 could be excellent candidates. We therefore determined the effects of aging and caloric restriction on the expression of FXR and TGR5 in the kidney. We found that FXR and TGR5 expression levels are decreased in the aging kidney and that caloric restriction prevents these age-related decreases. Interestingly, in long-lived Ames dwarf mice, renal FXR and TGR5 expression levels were also increased. A 2-month treatment of 22-month-old C57BL/6J mice with the FXR-TGR5 dual agonist INT-767 induced caloric restriction-like effects and reversed age-related increases in proteinuria, podocyte injury, fibronectin accumulation, TGF-β expression, and, most notably, age-related impairments in mitochondrial biogenesis and mitochondrial function. Furthermore, in podocytes cultured in serum obtained from old mice, INT-767 prevented the increases in the proinflammatory markers TNF-α, toll-like receptor 2 (TLR2), and TLR4. In summary, our results indicate that FXR and TGR5 may play an important role in modulation of age-related kidney disease.
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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.