ArticleProceedings of the National Academy of Sciences of the United States of America1999
The lack of a functional p21(WAF1/CIP1) gene ameliorates progression to chronic renal failure.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 124 citations in OpenAlex.
- From AKI to CKD mechanisms of maladaptive repair and disease progression.International urology and nephrology · 2026Review
- Chronic Kidney Disease and Cellular Senescence.International journal of molecular sciences · 2026Review
- Alterations in mitochondria and cellular senescence in aged sEH null female kidneys.GeroScience · 2026Article
- Energy depletion by cell proliferation sensitizes the kidney epithelial cells to injury.American journal of physiology. Renal physiology · 2024Article
- The interaction between cellular senescence and chronic kidney disease as a therapeutic opportunity.Frontiers in pharmacology · 2022Review
- Tubular Cell Cycle Response upon AKI: Revising Old and New Paradigms to Identify Novel Targets for CKD Prevention.International journal of molecular sciences · 2021Review
- Epithelial proliferation and cell cycle dysregulation in kidney injury and disease.Kidney international · 2021Review
- A clear pathway to tubulointerstitial disease: is an exclusive focus on fibrosis justified?The Journal of clinical investigation · 2021Article
- The Role of Ageing and Parenchymal Senescence on Macrophage Function and Fibrosis.Frontiers in immunology · 2021Review
- Cell Cycle Dysregulation and Renal Fibrosis.Frontiers in cell and developmental biology · 2021Review
- Acute Kidney Injury is Aggravated in Aged Mice by the Exacerbation of Proinflammatory Processes.Frontiers in pharmacology · 2021Article
- Signaling pathways predisposing to chronic kidney disease progression.JCI insight · 2020Article
- Metabolic Flexibility and Innate Immunity in Renal Ischemia Reperfusion Injury: The Fine Balance Between Adaptive Repair and Tissue Degeneration.Frontiers in immunology · 2020Review
- The p21 dependent G2 arrest of the cell cycle in epithelial tubular cells links to the early stage of renal fibrosis.Scientific reports · 2019Article
- TREM1/3 Deficiency Impairs Tissue Repair After Acute Kidney Injury and Mitochondrial Metabolic Flexibility in Tubular Epithelial Cells.Frontiers in immunology · 2019Article
- Renal fibrosis: Primacy of the proximal tubule.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
- Epithelial Cell Cycle Behaviour in the Injured Kidney.International journal of molecular sciences · 2018Review
- Acute Kidney Injury as a Condition of Renal Senescence.Cell transplantation · 2018Review
- Discoidin domain receptor 1 kinase activity is required for regulating collagen IV synthesis.Matrix biology : journal of the International Society for Matrix Biology · 2017Article
- Epithelial-to-mesenchymal transition induces cell cycle arrest and parenchymal damage in renal fibrosis.Nature medicine · 2015Article
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Abstract
Partial renal ablation leads to progressive renal insufficiency and is a model of chronic renal failure from diverse causes. We find that mice develop functional and morphologic characteristics of chronic renal failure after partial renal ablation, including glomerular sclerosis, systemic hypertension, and reduced glomerular filtration. However, we now report that littermates with a homozygous deletion of the gene for the cyclin-dependent kinase inhibitor, p21(WAF1/CIP1), do not develop chronic renal failure after ablation. The markedly different reactions of the p21(+/+) and p21(-/-) animals was not because of differences in glomerular number or degree of renal growth but rather because of the presence or absence of a normal p21 gene. Although the reaction to the stress of renal ablation is both hyperplastic and hypertrophic in the presence of a functional p21 gene, it would appear that the absence of the p21 gene may induce a more hyperplastic reaction because proliferating-cell nuclear antigen expression, a marker of cell-cycle progression, in the renal epithelium of the remnant kidney was more than five times greater in the p21(-/-) mice than in the p21(+/+) animals. Because p21 is a potent inhibitor of the cell cycle, we speculate that p21 regulates the balance between hyperplasia and hypertrophy after renal ablation. We propose that this change in response inhibits the development of chronic renal failure. These studies suggest that controlling p21 function may ameliorate or even prevent progressive end-stage renal disease.
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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 OpenQuestion graph.