ArticleEMBO reports2020
Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS.
Article in EMBO reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- TGF-β/Smad Signaling Pathway in Tubulointerstitial Fibrosis.Frontiers in pharmacology · 2022Pooled it
- Targeting mitochondrial quality control in diabetic kidney disease: emerging therapeutic opportunities.Renal failure · 2026Review
- ATPIF1, the rheostat in mitochondrial bioenergetics and dysfunction in diseases.Mitochondrion · 2026Review
- Renal glycogen handling in diabetes: A narrative review of diabetic kidney disease pathogenesis.Journal of diabetes investigation · 2026Review
- Arachidonic Acid Disrupts PKM2-Linked Glycolysis-Related Metabolism and Exacerbates PAN-Induced Podocyte Injury.Journal of cellular and molecular medicine · 2026Article
- The Role of Glycolysis in Diabetic Kidney Disease.International journal of molecular sciences · 2026Review
- Mitochondrial metabolic reprogramming drives diabetic kidney disease progression: cell-specific mechanisms, metabolic memory, and targeted strategies.Molecular medicine (Cambridge, Mass.) · 2026Review
- Podocyte Metabolic Reprogramming and Targeted Therapy.Journal of the American Society of Nephrology : JASN · 2026Review
- Modulation of Network Plasticity Opens Novel Therapeutic Possibilities in Cancer, Diabetes, and Neurodegeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Ethambutol induces optic neuropathy through SDHB-mediated ferroptosis in retinal ganglion cells via Smad4 pathway.Human cell · 2026Article
- Oxidative stress and endoplasmic reticulum stress in acute kidney injury: mechanistic crosstalk and therapeutic modulation.Frontiers in medicine · 2026Review
- Loss of glomerular aldolase B in diabetic nephropathy promotes renal fibrosis via activating Akt/GSK/β-catenin axis.Journal of advanced research · 2025Article
- sPLA2-IB and PLA2R Mediate Aberrant Glucose Metabolism in Podocytes via Hyperactivation of the mTOR/HIF-1α Pathway.Cell biochemistry and biophysics · 2025Article
- Targeting mitochondrial dysfunction: an innovative strategy for treating renal fibrosis.Molecular and cellular biochemistry · 2025Review
- The interplay between driver mutation and oxidative stress in colorectal cancer: from pathogenesis to therapeutics.Journal of translational medicine · 2025Review
- ACVR2A attenuation impacts lactate production and hyperglycolytic conditions attracting regulatory T cells in hepatocellular carcinoma.Cell reports. Medicine · 2025Article
- Nucleoporin-associated steroid-resistant nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2025Review
- Article
- Eye on the horizon: The metabolic landscape of the RPE in aging and disease.Progress in retinal and eye research · 2025Review
- Modulation of TGF-β signaling new approaches toward kidney disease and fibrosis therapy.International journal of biological sciences · 2025Review
Corrections and comments
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Authors and funding
24 authors at 10 institutions in 5 countries.
Funding
Abstract
Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease. TGF-β1/Smad3 signalling plays a major pathological role in DN; however, the contribution of Smad4 has not been examined. Smad4 depletion in the kidney using anti-Smad4 locked nucleic acid halted progressive podocyte damage and glomerulosclerosis in mouse type 2 DN, suggesting a pathogenic role of Smad4 in podocytes. Smad4 is upregulated in human and mouse podocytes during DN. Conditional Smad4 deletion in podocytes protects mice from type 2 DN, independent of obesity. Mechanistically, hyperglycaemia induces Smad4 localization to mitochondria in podocytes, resulting in reduced glycolysis and oxidative phosphorylation and increased production of reactive oxygen species. This operates, in part, via direct binding of Smad4 to the glycolytic enzyme PKM2 and reducing the active tetrameric form of PKM2. In addition, Smad4 interacts with ATPIF1, causing a reduction in ATPIF1 degradation. In conclusion, we have discovered a mitochondrial mechanism by which Smad4 causes diabetic podocyte injury.
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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.