ArticleDiabetes & metabolism journal2020
Fibroblast Growth Factor 21 Attenuates Diabetes-Induced Renal Fibrosis by Negatively Regulating TGF-β-p53-Smad2/3-Mediated Epithelial-to-Mesenchymal Transition via Activation of AKT.
Article in Diabetes & metabolism journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 49 citations in OpenAlex.
- IL-15 Links Muscle-Kidney Crosstalk to Preserving Podocyte Mitochondrial Fusion and Attenuating Diabetic Nephropathy.Journal of cachexia, sarcopenia and muscle · 2026Article
- Diabetes and its complications: molecular mechanisms, prevention and treatment.Signal transduction and targeted therapy · 2026Review
- Plasma PZP level elevation: a potential correlate of diabetic kidney disease progression.Frontiers in medicine · 2026Article
- Elevation of p53 sensitizes obese kidney to adriamycin-induced aberrant lipid homeostasis via repressing HNF4α-mediated FGF21 sensitivity.Journal of advanced research · 2025Article
- Review
- MAP3K19 Promotes the Progression of Tuberculosis-Induced Pulmonary Fibrosis Through Activation of the TGF-β/Smad2 Signaling Pathway.Molecular biotechnology · 2024Article
- Myostatin regulates energy homeostasis through autocrine- and paracrine-mediated microenvironment communication.The Journal of clinical investigation · 2024Article
- FGF21 Inhibits Hypoxia/Reoxygenation-induced Renal Tubular Epithelial Cell Injury by Regulating the PPARγ/NF-κB Signaling Pathway.Cell biochemistry and biophysics · 2024Article
- Exercise alleviates renal interstitial fibrosis by ameliorating the Sirt1-mediated TGF-β1/Smad3 pathway in T2DM mice.Endocrine connections · 2024Article
- Urinary Excretion of Biomolecules Related to Cell Cycle, Proliferation, and Autophagy in Subjects with Type 2 Diabetes and Chronic Kidney Disease.Biomedicines · 2024Article
- Cadherin-responsive hydrogel combined with dental pulp stem cells and fibroblast growth factor 21 promotes diabetic scald repair via regulating epithelial-mesenchymal transition and necroptosis.Materials today. Bio · 2024Article
- Advances in the Treatment of Kidney Disorders using Mesenchymal Stem Cells.Current pharmaceutical design · 2024Review
- Evaluation of serum pro/anti-angiogenic biomarkers in hyperglycemic rats treated withJournal of cardiovascular and thoracic research · 2024Article
- Myokines: Novel therapeutic targets for diabetic nephropathy.Frontiers in endocrinology · 2022Review
- Research Progress of Fibroblast Growth Factor 21 in Fibrotic Diseases.Oxidative medicine and cellular longevity · 2022Review
- Fibroblast Growth Factor 21 Predicts Short-Term Prognosis in Patients With Acute Heart Failure: A Prospective Cohort Study.Frontiers in cardiovascular medicine · 2022Article
- Phosphate Toxicity and Epithelial to Mesenchymal Transition.Advances in experimental medicine and biology · 2022Article
- Exercise Training Alleviates Cardiac Fibrosis through Increasing Fibroblast Growth Factor 21 and Regulating TGF-β1-Smad2/3-MMP2/9 Signaling in Mice with Myocardial Infarction.International journal of molecular sciences · 2021Article
- FOXN3 inhibits cell proliferation and invasion via modulating the AKT/MDM2/p53 axis in human glioma.Aging · 2021Article
- FGF21 prevents low-protein diet-induced renal inflammation in aged mice.American journal of physiology. Renal physiology · 2021Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEpithelial-to-mesenchymal transition (EMT) is required for renal fibrosis, which is a characteristic of diabetic nephropathy (DN). Our previous study demonstrated that fibroblast growth factor 21 (FGF21) prevented DN associated with the suppressing renal connective tissue growth factor expression, a key marker of renal fibrosis. Therefore, the effects of FGF21 on renal fibrosis in a DN mouse model and the underlying mechanisms were investigated in this study.
methodsType 1 diabetes mellitus was induced in C57BL/6J mice by intraperitoneal injections of multiple low doses of streptozotocin. Then, diabetic and non-diabetic mice were treated with or without FGF21 in the presence of pifithrin-α (p53 inhibitor) or 10-[4'-(N,N-Diethylamino)butyl]-2-chlorophenoxazine hydrochloride (10-DEBC) hydrochloride (Akt inhibitor) for 4 months.
resultsDN was diagnosed by renal dysfunction, hypertrophy, tubulointerstitial lesions, and glomerulosclerosis associated with severe fibrosis, all of which were prevented by FGF21. FGF21 also suppressed the diabetes-induced renal EMT in DN mice by negatively regulating transforming growth factor beta (TGF-β)-induced nuclear translocation of Smad2/3, which is required for the transcription of multiple fibrotic genes. The mechanistic studies showed that FGF21 attenuated nuclear translocation of Smad2/3 by inhibiting renal activity of its conjugated protein p53, which carries Smad2/3 into the nucleus. Moreover pifithrin-α inhibited the FGF21-induced preventive effects on the renal EMT and subsequent renal fibrosis in DN mice. In addition, 10-DEBC also blocked FGF21-induced inhibition of renal p53 activity by phosphorylation of mouse double minute-2 homolog (MDM2).
conclusionFGF21 prevents renal fibrosis via negative regulation of the TGF-β/Smad2/3-mediated EMT process by activation of the Akt/MDM2/p53 signaling pathway.
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