ArticleOncotarget2017
Pharmacologic targeting ERK1/2 attenuates the development and progression of hyperuricemic nephropathy in rats.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Serum uric acid and its metabolism-a vital factor in the inflammatory transformation of cancer.Journal of advanced research · 2026Review
- The role of ERK1/2 signaling in diabetes: pathogenic and therapeutic implications.Frontiers in pharmacology · 2025Review
- Recent Advances on the Regulations of Organic Anion Transporters.Pharmaceutics · 2024Review
- Article
- Renal Organic Anion Transporters 1 and 3 In Vitro: Gone but Not Forgotten.International journal of molecular sciences · 2023Review
- A Review on Extracts, Chemical Composition and Product Development of WalnutFoods (Basel, Switzerland) · 2023Review
- Article
- The dysregulation of immune cells induced by uric acid: mechanisms of inflammation associated with hyperuricemia and its complications.Frontiers in immunology · 2023Review
- Effects of Acute 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Exposure on the Circulating and Cecal Metabolome Profile.International journal of molecular sciences · 2021Article
- The Rho kinase signaling pathway participates in tubular mitochondrial oxidative injury and apoptosis in uric acid nephropathy.The Journal of international medical research · 2021Article
- The roles of NLRP3 inflammasome-mediated signaling pathways in hyperuricemic nephropathy.Molecular and cellular biochemistry · 2021Review
- Pharmacologic Targeting of BET Proteins Attenuates Hyperuricemic Nephropathy in Rats.Frontiers in pharmacology · 2021Article
- Drug Transporters in the Kidney: Perspectives on Species Differences, Disease Status, and Molecular Docking.Frontiers in pharmacology · 2021Review
- Emerging Therapeutic Strategies for Attenuating Tubular EMT and Kidney Fibrosis by Targeting Wnt/β-Catenin Signaling.Frontiers in pharmacology · 2021Review
- Delayed treatment with an autophagy inhibitor 3-MA alleviates the progression of hyperuricemic nephropathy.Cell death & disease · 2020Article
- Treatment with a PPAR-γ Agonist Protects Against Hyperuricemic Nephropathy in a Rat Model.Drug design, development and therapy · 2020Article
- Induction of Fibrogenic Phenotype in Human Mesenchymal Stem Cells by Connective Tissue Growth Factor in a Hydrogel Model of Soft Connective Tissue.ACS biomaterials science & engineering · 2019Article
- Blockade of ERK1/2 by U0126 alleviates uric acid-induced EMT and tubular cell injury in rats with hyperuricemic nephropathy.American journal of physiology. Renal physiology · 2019Article
- Blockade of enhancer of zeste homolog 2 alleviates renal injury associated with hyperuricemia.American journal of physiology. Renal physiology · 2019Article
- The MEK Inhibitor Trametinib Ameliorates Kidney Fibrosis by Suppressing ERK1/2 and mTORC1 Signaling.Journal of the American Society of Nephrology : JASN · 2019Article
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pathogenesis of hyperuricemia-induced chronic kidney disease is largely unknown. In this study, we investigated whether extracellular signal-regulated kinases1/2 (ERK1/2) would contribute to the development of hyperuricemic nephropathy (HN). In a rat model of HN induced by feeding mixture of adenine and potassium oxonate, increased ERK1/2 phosphorylation and severe glomerular sclerosis and renal interstitial fibrosis were evident, in parallel with diminished levels of renal function and increased urine microalbumin excretion. Administration of U0126, which is a selective inhibitor of the ERK1/2 pathway, improved renal function, decreased urine microalbumin and inhibited activation of renal interstitial fibroblasts as well as accumulation of extracellular proteins. U0126 also inhibited hyperuricemia-induced expression of multiple profibrogenic cytokines/chemokines and infiltration of macrophages in the kidney. Furthermore, U0126 treatment suppressed xanthine oxidase, which mediates uric acid production. It also reduced expression of the urate anion exchanger 1, which promotes reabsorption of uric acid, and preserved expression of organic anion transporters 1 and 3, which accelerate uric acid excretion in the kidney of hyperuricemic rats. Finally, U0126 inhibited phosphorylation of Smad3, a key mediator in transforming growth factor (TGF-β) signaling. In cultured renal interstitial fibroblasts, inhibition of ERK1/2 activation by siRNA suppressed uric acid-induced activation of renal interstitial fibroblasts. Collectively, pharmacologic targeting of ERK1/2 can alleviate HN by suppressing TGF-β signaling, reducing inflammation responses, and inhibiting the molecular processes associated with elevation of blood uric acid levels in the body. Thus, ERK1/2 inhibition may be a potential approach for the prevention and treatment of hyperuricemic nephropathy.
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