ArticleAmerican journal of physiology. Renal physiology2015
AMP-activated protein kinase (AMPK) activation inhibits nuclear translocation of Smad4 in mesangial cells and diabetic kidneys.
Article in American journal of physiology. Renal physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 50 citations in OpenAlex.
- From fat to filter: the effect of adipose tissue-derived signals on kidney function.Nature reviews. Nephrology · 2025Review
- AMPK pathway: an emerging target to control diabetes mellitus and its related complications.Journal of diabetes and metabolic disorders · 2024Review
- [The Role of TGF-β1/SMAD in Diabetic Nephropathy: Mechanisms and Research Development].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2023Article
- 14, 15-EET alleviates neurological impairment through maintaining mitochondrial dynamics equilibrium via AMPK/SIRT1/FoxO1 signal pathways in mice with cerebral ischemia reperfusion.CNS neuroscience & therapeutics · 2023Article
- Suramin prevents the development of diabetic kidney disease by inhibiting NLRP3 inflammasome activation in KK-Ay mice.Journal of diabetes investigation · 2023Article
- MicroRNA-10a/b inhibit TGF-β/Smad-induced renal fibrosis by targeting TGF-β receptor 1 in diabetic kidney disease.Molecular therapy. Nucleic acids · 2022Article
- Impact of adiposity on risk of female gout among those genetically predisposed: sex-specific prospective cohort study findings over >32 years.Annals of the rheumatic diseases · 2022Article
- A spotlight on underlying the mechanism of AMPK in diabetes complications.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Review
- Mitochondrial remodelling-a vicious cycle in diabetic complications.Molecular biology reports · 2021Review
- TGF-β: The missing link in obesity-associated airway diseases?Current research in pharmacology and drug discovery · 2021Review
- Restoring mitochondrial superoxide levels with elamipretide (MTP-131) protectsThe Journal of biological chemistry · 2020Article
- Smad4 promotes diabetic nephropathy by modulating glycolysis and OXPHOS.EMBO reports · 2020Article
- Mechanisms of Herbal Nephroprotection in diabetes mellitus.Journal of diabetes research · 2020Review
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- Coreopsis tinctoria Nutt ameliorates high glucose-induced renal fibrosis and inflammation via the TGF-β1/SMADS/AMPK/NF-κB pathways.BMC complementary and alternative medicine · 2019Article
- Thalidomide decreases high glucose-induced extracellular matrix protein synthesis in mesangial cells via the AMPK pathway.Experimental and therapeutic medicine · 2019Article
- Wedelolactone Attenuates Pulmonary Fibrosis Partly Through Activating AMPK and Regulating Raf-MAPKs Signaling Pathway.Frontiers in pharmacology · 2019Article
- Alpha-Mangostin Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Mice Partly Through Activating Adenosine 5'-Monophosphate-Activated Protein Kinase.Frontiers in pharmacology · 2019Article
- Dietary Leucine Supplement Ameliorates Hepatic Steatosis and Diabetic Nephropathy in db/db Mice.International journal of molecular sciences · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Diabetic nephropathy is characterized by diffuse mesangial matrix expansion and is largely dependent on the TGF-β/Smad signaling pathway. Smad4 is required for TGF-β signaling; however, its regulation has not been well characterized in diabetic kidney disease. Here, we report that high glucose is sufficient to stimulate nuclear translocation of Smad4 in mesangial cells and that stimulation of the major energy sensor AMP-activated protein kinase (AMPK) has a potent effect to block Smad4 nuclear translocation. Activation of AMPK by 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) inhibited high glucose-induced and TGF-β stimulation of nuclear Smad4. To identify which of the catalytic α-subunits may be involved, small interfering (si) RNA-based inhibition of AMPK α1- or α2-subunit was employed. Inhibition of either subunit reduced overall AMPK activity and contributed to Smad4 nuclear accumulation. In an animal model of early diabetic kidney disease, induction of diabetes was found to markedly stimulate Smad4 protein levels and enhance nuclear accumulation. AMPK activation with AICAR completely prevented the upregulation of Smad4 and reduced mesangial matrix accumulation. We conclude that stimulation of Smad4 in cell culture and in in vivo models of early diabetic kidney disease is dependent on AMPK.
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