ArticleJournal of the American Society of Nephrology : JASN2019
The MEK Inhibitor Trametinib Ameliorates Kidney Fibrosis by Suppressing ERK1/2 and mTORC1 Signaling.
Article in Journal of the American Society of Nephrology : JASN, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed.
- Repurposing the MEK inhibitor binimetinib as a dual anti-inflammatory and antifibrotic agent in pulmonary fibrosis.Journal of thoracic disease · 2026Article
- Review
- Article
- TGF-β1 induces ROS to activate ferroptosis via the ERK1/2-WISP1 pathway to promote the progression of renal tubular epithelial cell fibrosis.Cytotechnology · 2025Article
- Update of cellular senescence in kidney fibrosis: from mechanism to potential interventions.Frontiers of medicine · 2025Review
- Artesunate alleviates kidney fibrosis by restoring klotho protein and suppressing Wnt/β-catenin signalling pathway.Frontiers in cell and developmental biology · 2025Article
- Targeting Fibrosis: From Molecular Mechanisms to Advanced Therapies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Emodin inhibits M1 macrophage activation that related to acute and chronic kidney injury through EGFR/MAPK pathway.Functional & integrative genomics · 2024Article
- Efficacy of Trametinib in Alleviating Cisplatin-Induced Acute Kidney Injury: Inhibition of Inflammation, Oxidative Stress, and Tubular Cell Death in a Mouse Model.Molecules (Basel, Switzerland) · 2024Article
- Rictor/mTORC2 signalling contributes to renal vascular endothelial-to-mesenchymal transition and renal allograft interstitial fibrosis by regulating BNIP3-mediated mitophagy.Clinical and translational medicine · 2024Article
- A MEK inhibitor arrests the cell cycle of human conjunctival fibroblasts and improves the outcome of glaucoma filtration surgery.Scientific reports · 2024Article
- Cep120 is essential for kidney stromal progenitor cell growth and differentiation.EMBO reports · 2024Article
- Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide.Nature communications · 2023Article
- Basement membrane proteins in extracellular matrix characterize NF1 neurofibroma development and response to MEK inhibitor.The Journal of clinical investigation · 2023Article
- Salvianolic Acid A Improves Rat Kidney Injury by Regulating MAPKs and TGF-β1/Smads Signaling Pathways.Molecules (Basel, Switzerland) · 2023Article
- DNA-dependent protein kinase catalytic subunit (DNA-PKcs) drives chronic kidney disease progression in male mice.Nature communications · 2023Article
- Dual inhibition of the MEK/ERK and PI3K/AKT pathways prevents pulmonary GVHD suppressing perivenulitis and bronchiolitis.Blood advances · 2023Article
- Vaccination against connective tissue growth factor attenuates the development of renal fibrosis.Scientific reports · 2022Article
- In Vivo Inhibition of TRPC6 by SH045 Attenuates Renal Fibrosis in a New Zealand Obese (NZO) Mouse Model of Metabolic Syndrome.International journal of molecular sciences · 2022Article
- Advancements in nanomedicines for the detection and treatment of diabetic kidney disease.Biomaterials and biosystems · 2022Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
backgroundDuring kidney fibrosis, a hallmark and promoter of CKD (regardless of the underlying renal disorder leading to CKD), the extracellular-regulated kinase 1/2 (ERK1/2) pathway, is activated and has been implicated in the detrimental differentiation and expansion of kidney fibroblasts. An ERK1/2 pathway inhibitor, trametinib, is currently used in the treatment of melanoma, but its efficacy in the setting of CKD and renal fibrosis has not been explored.
methodsWe investigated whether trametinib has antifibrotic effects in two mouse models of renal fibrosis-mice subjected to unilateral ureteral obstruction (UUO) or fed an adenine-rich diet-as well as in cultured primary human fibroblasts. We also used immunoblot analysis, immunohistochemical staining, and other tools to study underlying molecular mechanisms for antifibrotic effects.
resultsTrametinib significantly attenuated collagen deposition and myofibroblast differentiation and expansion in UUO and adenine-fed mice. We also discovered that in injured kidneys, inhibition of the ERK1/2 pathway by trametinib ameliorated mammalian target of rapamycin complex 1 (mTORC1) activation, another key profibrotic signaling pathway. Trametinib also inhibited the ERK1/2 pathway in cultured primary human renal fibroblasts stimulated by application of TGF-
conclusionsFurther study of trametinib as a potential candidate for the treatment of chronic renal fibrotic diseases of diverse etiologies is warranted.
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