ArticleProceedings of the National Academy of Sciences of the United States of America2015
Mitigation of acute kidney injury by cell-cycle inhibitors that suppress both CDK4/6 and OCT2 functions.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 107 citations in OpenAlex.
- Incidence and Magnitude of Pseudo-decrease in Kidney Function With Oral Epidermal Growth Factor Inhibitor Osimertinib.Kidney medicine · 2026Article
- Apoptosis and Cell Cycle Dysregulation in AmpligoJournal of xenobiotics · 2026Article
- Matricellular protein SMOC2 safeguards tubular integrity in acute kidney injury via integrin β3-dependent inhibition of CCND1-CDK4/6 axis.Molecular biomedicine · 2026Article
- A Novel Functional Method of Protector Screening for Zebrafish Lateral Line Hair Cells via the Acoustic Escape Response.Neuroscience bulletin · 2025Article
- Drug-Drug Interaction Liabilities with BTK Inhibitor TL-895.Cancer research communications · 2025Article
- Cellular senescence in renal ischemia-reperfusion injury.Chinese medical journal · 2025Review
- Pseudo acute kidney injury in patients receiving CDK4/6 inhibitors.British journal of cancer · 2025Article
- Resazurin dye is an in vivo sensor of kidney tubular function.Kidney international · 2025Article
- CDK4 inactivation inhibits apoptosis via mitochondria-ER contact remodeling in triple-negative breast cancer.Nature communications · 2025Article
- A Newly Identified Protective Role of C5a Receptor 1 in Kidney Tubules against Toxin-Induced Acute Kidney Injury.The American journal of pathology · 2025Article
- The deleterious effects of CDK4/6 inhibition on renal recovery post-acute kidney injury.Scientific reports · 2024Article
- Proton Pump Inhibitors May Cause a Decline in eGFR by Inhibiting Organic Cation Transporter 2-Dependent Creatinine Secretion.Journal of the American Society of Nephrology : JASN · 2024Article
- Systematic Evaluation of Tyrosine Kinase Inhibitors as OATP1B1 Substrates Using a Competitive Counterflow Screen.Cancer research communications · 2024Article
- Renal tubular epithelial cells response to injury in acute kidney injury.EBioMedicine · 2024Review
- From Acute to Chronic: Unraveling the Pathophysiological Mechanisms of the Progression from Acute Kidney Injury to Acute Kidney Disease to Chronic Kidney Disease.International journal of molecular sciences · 2024Review
- Dabrafenib protects from cisplatin-induced hearing loss in a clinically relevant mouse model.JCI insight · 2023Article
- Mouse and human studies support DSTYK loss of function as a low-penetrance and variable expressivity risk factor for congenital urinary tract anomalies.Genetics in medicine : official journal of the American College of Medical Genetics · 2023Article
- The Therapeutic Potential of CDK4/6 Inhibitors, Novel Cancer Drugs, in Kidney Diseases.International journal of molecular sciences · 2023Review
- Role of Mouse Organic Cation Transporter 2 for Nephro- and Peripheral Neurotoxicity Induced by Chemotherapeutic Treatment with Cisplatin.International journal of molecular sciences · 2023Article
- Zinc finger protein 24-dependent transcription factor SOX9 up-regulation protects tubular epithelial cells during acute kidney injury.Kidney international · 2023Article
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Authors and funding
14 authors at 1 institution in 1 country.
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Abstract
Acute kidney injury (AKI) is a potentially fatal syndrome characterized by a rapid decline in kidney function caused by ischemic or toxic injury to renal tubular cells. The widely used chemotherapy drug cisplatin accumulates preferentially in the renal tubular cells and is a frequent cause of drug-induced AKI. During the development of AKI the quiescent tubular cells reenter the cell cycle. Strategies that block cell-cycle progression ameliorate kidney injury, possibly by averting cell division in the presence of extensive DNA damage. However, the early signaling events that lead to cell-cycle activation during AKI are not known. In the current study, using mouse models of cisplatin nephrotoxicity, we show that the G1/S-regulating cyclin-dependent kinase 4/6 (CDK4/6) pathway is activated in parallel with renal cell-cycle entry but before the development of AKI. Targeted inhibition of CDK4/6 pathway by small-molecule inhibitors palbociclib (PD-0332991) and ribociclib (LEE011) resulted in inhibition of cell-cycle progression, amelioration of kidney injury, and improved overall survival. Of additional significance, these compounds were found to be potent inhibitors of organic cation transporter 2 (OCT2), which contributes to the cellular accumulation of cisplatin and subsequent kidney injury. The unique cell-cycle and OCT2-targeting activities of palbociclib and LEE011, combined with their potential for clinical translation, support their further exploration as therapeutic candidates for prevention of AKI.
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