ArticleAmerican journal of physiology. Renal physiology2014
CDK4/6 inhibition induces epithelial cell cycle arrest and ameliorates acute kidney injury.
Article in American journal of physiology. Renal physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 118 citations in OpenAlex.
- Molecular modulators of cyclin-dependent kinase 4/6 inhibitor response in experimental glioma identified through genome-wide CRISPR-Cas9 screening.Neuro-oncology · 2026Article
- Targeting YAP1-Mediated Tubular Cell Senescence to Attenuate Maladaptive Repair and Fibrotic Transition After Acute Kidney Injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Article
- Transition from acute kidney injury to chronic kidney disease: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Proximal TGF-β Signaling in Chronic Injury: from a notorious fibrotic factor to a repair ally.Pflugers Archiv : European journal of physiology · 2026Review
- Dual Roles and Therapeutic Prospects of Proximal Tubular Epithelial Cell Senescence in Acute Kidney Injury.Biomolecules · 2026Review
- Pathophysiology and Management of Sepsis-associated Acute Kidney Injury.Clinics in chest medicine · 2026Review
- Matricellular protein SMOC2 safeguards tubular integrity in acute kidney injury via integrin β3-dependent inhibition of CCND1-CDK4/6 axis.Molecular biomedicine · 2026Article
- Longitudinal Multi-Organ Transcriptomic Atlas of Salt-Induced Hypertension.bioRxiv : the preprint server for biology · 2025Article
- Cellular senescence in renal ischemia-reperfusion injury.Chinese medical journal · 2025Review
- JMJD3-mediated senescence is required to overcome stress-induced hematopoietic defects.EMBO reports · 2025Article
- ANKHD1 promotes pathogenic proliferation in Autosomal Dominant Polycystic Kidney Disease via the Cyclin D1/CDK4 pathway.Journal of translational medicine · 2025Article
- CDK4 inactivation inhibits apoptosis via mitochondria-ER contact remodeling in triple-negative breast cancer.Nature communications · 2025Article
- Renal aging and its consequences: navigating the challenges of an aging population.Frontiers in pharmacology · 2025Review
- Urinary proteomics identifies distinct immunological profiles of sepsis associated AKI sub-phenotypes.Critical care (London, England) · 2024Article
- The deleterious effects of CDK4/6 inhibition on renal recovery post-acute kidney injury.Scientific reports · 2024Article
- Nanotherapeutic kidney cell-specific targeting to ameliorate acute kidney injury.Kidney international · 2024Article
- Renal tubular epithelial cells response to injury in acute kidney injury.EBioMedicine · 2024Review
- Systemic oncological therapy in breast cancer patients on dialysis.World journal of clinical oncology · 2024Review
- Rac1 promotes kidney collecting duct repair by mechanically coupling cell morphology to mitotic entry.Science advances · 2024Article
16 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Acute kidney injury (AKI) is common and urgently requires new preventative therapies. Expression of a cyclin-dependent kinase (CDK) inhibitor transgene protects against AKI, suggesting that manipulating the tubular epithelial cell cycle may be a viable therapeutic strategy. Broad spectrum small molecule CDK inhibitors are protective in some kidney injury models, but these have toxicities and epithelial proliferation is eventually required for renal repair. Here, we tested a well-tolerated, novel and specific small molecule inhibitor of CDK4 and CDK6, PD 0332991, to investigate the effects of transient cell cycle inhibition on epithelial survival in vitro and kidney injury in vivo. We report that CDK4/6 inhibition induced G0/G1 cycle arrest in cultured human renal proximal tubule cells (hRPTC) at baseline and after injury. Induction of transient G0/G1 cycle arrest through CDK4/6 inhibition protected hRPTC from DNA damage and caspase 3/7 activation following exposure to the nephrotoxins cisplatin, etoposide, and antimycin A. In vivo, mice treated with PD 0332991 before ischemia-reperfusion injury (IRI) exhibited dramatically reduced epithelial progression through S phase 24 h after IRI. Despite reduced epithelial proliferation, PD 0332991 ameliorated kidney injury as reflected by improved serum creatinine and blood urea nitrogen levels 24 h after injury. Inflammatory markers and macrophage infiltration were significantly decreased in injured kidneys 3 days following IRI. These results indicate that induction of proximal tubule cell cycle arrest with specific CDK4/6 inhibitors, or "pharmacological quiescence," represents a novel strategy to prevent AKI.
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