ArticleJCI insight2022
Blocking cell cycle progression through CDK4/6 protects against chronic kidney disease.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- GADD45A may be a potential biomarker associated with endoplasmic reticulum stress in focal segmental glomerulosclerosis.Biochemistry and biophysics reports · 2026Article
- Magnesium Attenuates Renal Senescence and Fibrosis With Reduced DNA Damage Response and H3K4me3 Enrichment at the p16FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- miR-21-5p Alleviates Retinal Ischemia-Reperfusion Injury by Inhibiting M1 Polarization of Microglia via Suppression of STAT3 Signaling.Biomedicines · 2025Article
- ANKHD1 promotes pathogenic proliferation in Autosomal Dominant Polycystic Kidney Disease via the Cyclin D1/CDK4 pathway.Journal of translational medicine · 2025Article
- Targeted multi-layer analysis of PANoptosis-associated genes in the etiology of chronic kidney disease.Human genomics · 2025Article
- Targeting MLL1/WDR5-Mediated Epigenetic Regulation Mitigates Peritoneal Fibrosis by Reducing p16FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Assays to enhance metabolic phenotyping in the kidney.American journal of physiology. Renal physiology · 2025Article
- Accelerators of chronic hepatitis B fibrosis cirrhosis CCND1 gene expression and promoter hypomethylation.Scientific reports · 2025Article
- Biology of the proximal tubule in body homeostasis and kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Review
- CDK4 inactivation inhibits apoptosis via mitochondria-ER contact remodeling in triple-negative breast cancer.Nature communications · 2025Article
- Integrative analysis of m6A-SNPs and single-cell RNA sequencing reveals key drivers of endocrine combined with CDK4/6 inhibitor therapy resistance in ER+ breast cancer.Frontiers in pharmacology · 2025Article
- HACE1 as a bridge between oxidative stress and autophagy.Frontiers in immunology · 2025Review
- Unbiased kinome profiling identifies key and novel mediators of chronic kidney disease in hyperlipidemic mice.Frontiers in physiology · 2025Article
- The deleterious effects of CDK4/6 inhibition on renal recovery post-acute kidney injury.Scientific reports · 2024Article
- Selective activation of PPARα by pemafibrate mitigates peritoneal inflammation and fibrosis through suppression of NLRP3 inflammasome and modulation of inflammation.Scientific reports · 2024Article
- Role of the CDKL1-SOX11 signaling axis in acute kidney injury.American journal of physiology. Renal physiology · 2024Article
- Article
- Rac1 promotes kidney collecting duct repair by mechanically coupling cell morphology to mitotic entry.Science advances · 2024Article
- The Therapeutic Potential of CDK4/6 Inhibitors, Novel Cancer Drugs, in Kidney Diseases.International journal of molecular sciences · 2023Review
- The Sympathetic Nervous System Regulates Sodium Glucose Co-Transporter 1 Expression in the Kidney.Biomedicines · 2023Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Acute and chronic kidney injuries induce increased cell cycle progression in renal tubules. While increased cell cycle progression promotes repair after acute injury, the role of ongoing tubular cell cycle progression in chronic kidney disease is unknown. Two weeks after initiation of chronic kidney disease, we blocked cell cycle progression at G1/S phase by using an FDA-approved, selective inhibitor of CDK4/6. Blocking CDK4/6 improved renal function and reduced tubular injury and fibrosis in 2 murine models of chronic kidney disease. However, selective deletion of cyclin D1, which complexes with CDK4/6 to promote cell cycle progression, paradoxically increased tubular injury. Expression quantitative trait loci (eQTLs) for CCND1 (cyclin D1) and the CDK4/6 inhibitor CDKN2B were associated with eGFR in genome-wide association studies. Consistent with the preclinical studies, reduced expression of CDKN2B correlated with lower eGFR values, and higher levels of CCND1 correlated with higher eGFR values. CDK4/6 inhibition promoted tubular cell survival, in part, through a STAT3/IL-1β pathway and was dependent upon on its effects on the cell cycle. Our data challenge the paradigm that tubular cell cycle progression is beneficial in the context of chronic kidney injury. Unlike the reparative role of cell cycle progression following acute kidney injury, these data suggest that blocking cell cycle progression by inhibiting CDK4/6, but not cyclin D1, protects against chronic kidney injury.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.