ArticleScientific reports2016
Activation of FXR protects against renal fibrosis via suppressing Smad3 expression.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 61 citations in OpenAlex.
- Genetic contributions to lupus nephritis in a multi-ethnic cohort of systemic lupus erythematous patients.PloS one · 2018Trial
- Benzoxazole Derivatives as Potent FXR and PPARα Dual Agonists With Anti-Fibrotic and Metabolic Regulatory Effects.MedComm · 2025Article
- Identification of immunometabolism-associated genes and immune infiltration in sepsis-induced cardiomyopathy using integrated bioinformatics and machine learning approaches.The Journal of international medical research · 2025Article
- Role of nuclear receptors, lipid metabolism, and mitochondrial function in the pathogenesis of diabetic kidney disease.American journal of physiology. Renal physiology · 2025Review
- The role of the farnesoid X receptor in diabetes and its complications.Molecular and cellular biochemistry · 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
- Artesunate alleviates kidney fibrosis by restoring klotho protein and suppressing Wnt/β-catenin signalling pathway.Frontiers in cell and developmental biology · 2025Article
- Research progress in the treatment of lipid metabolism disorder in patients with diabetic kidney disease by the integrated traditional Chinese and Western medicine.Frontiers in endocrinology · 2025Review
- Bioactive metabolites: A clue to the link between MASLD and CKD?Clinical and molecular hepatology · 2025Review
- Role of Bile Acid Receptors in the Development and Function of Diabetic Nephropathy.Kidney international reports · 2024Review
- Farnesoid X receptor prevents neutrophil extracellular traps via reduced sphingosine-1-phosphate in chronic kidney disease.American journal of physiology. Renal physiology · 2023Article
- Kidney lipid dysmetabolism and lipid droplet accumulation in chronic kidney disease.Nature reviews. Nephrology · 2023Review
- YAP/TAZ: Molecular pathway and disease therapy.MedComm · 2023Review
- Regulon analysis identifies protective FXR and CREB5 in proximal tubules in early diabetic kidney disease.BMC nephrology · 2023Article
- Article
- The role of the farnesoid X receptor in kidney health and disease: a potential therapeutic target in kidney diseases.Experimental & molecular medicine · 2023Review
- EDP-297: A novel, farnesoid X receptor agonist-Results of a phase I study in healthy subjects.Clinical and translational science · 2023Article
- Role of FXR in Renal Physiology and Kidney Diseases.International journal of molecular sciences · 2023Review
- Bile Acid Network and Vascular Calcification-Associated Diseases: Unraveling the Intricate Connections and Therapeutic Potential.Clinical interventions in aging · 2023Review
- Dual soluble epoxide hydrolase inhibitor - farnesoid X receptor agonist interventional treatment attenuates renal inflammation and fibrosis.Frontiers in immunology · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Renal fibrosis is the common pathway of most chronic kidney disease progression to end-stage renal failure. The nuclear receptor FXR (farnesoid X receptor), a multiple functional transcription factor, plays an important role in protecting against fibrosis. The TGFβ-Smad signaling has a central role in kidney fibrosis. However, it remains unclear whether FXR plays direct anti-fibrotic effect in renal fibrosis via regulating TGFβ-Smad pathway. In this study, we found that the level of FXR was negatively correlated with that of Smad3 and fibronectin (a marker of fibrosis) in human fibrotic kidneys. Activation of FXR suppressed kidney fibrosis and downregulated Smad3 expression, which was markedly attenuated by FXR antagonist. Moreover, the FXR-mediated repression of fibrosis was significantly alleviated by ectopic expression of Smad3. Luciferase reporter assay revealed that FXR activation inhibited the transcriptional activity of Smad3 gene promoter. The in vivo experiments showed that FXR agonist protected against renal fibrosis and downregulated Smad3 expression in UUO mice. These results suggested that FXR may serve as an important negative regulator for manipulating Smad3 expression, and the FXR/Smad3 pathway may be a novel target for the treatment of renal fibrosis.
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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.