ArticleThe Journal of clinical investigation2022
Cyclin G1 induces maladaptive proximal tubule cell dedifferentiation and renal fibrosis through CDK5 activation.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 43 citations in OpenAlex.
- Involvement of impaired carnitine-induced fatty acid oxidation in experimental and human diabetic kidney disease.JCI insight · 2025Trial
- SMOC2 promotes partial epithelial-mesenchymal transition and maladaptive repair in renal tubular epithelial cells.JCI insight · 2026Article
- Mechanisms of regeneration and maladaptive repair in acute kidney injury.Nature reviews. Nephrology · 2026Review
- Sustained tenascin-C activation drives AKI-to-CKD progression via the Wnt/β-catenin pathway.International urology and nephrology · 2026Article
- Modelling ischaemic AKI in human kidney organoids reveals injury-associated epithelial states and macrophage-epithelial crosstalk.Genome medicine · 2026Article
- Proteomic Characterization of Replication Stress and Impaired Antioxidant Defense in Tacrolimus-Induced Chronic Nephrotoxicity.International journal of molecular sciences · 2026Article
- Transition from acute kidney injury to chronic kidney disease: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Identification of shared diagnostic biomarkers and molecular pathways between chronic kidney disease and renal cell carcinoma using transcriptomics and machine learning.Translational cancer research · 2026Article
- DYRK2 drives renal fibrosis through CDK1-dependent G2/M phase dysregulation in tubular epithelial cells.Cellular & molecular biology letters · 2026Article
- Monitoring biological effects of somatic cell genome editing.Nature reviews. Genetics · 2026Review
- Mitigation of Ischemia/Reperfusion-Induced Acute Kidney Injury by Canagliflozin Is Associated with Altered Mitochondrial Dynamics and Reduced Proliferation in Swine.Biomolecules · 2026Article
- Article
- Immunoreceptor CD300a regulates ischemic tissue damage and adverse remodeling in the mouse heart and kidney.The Journal of clinical investigation · 2025Article
- Krüppel-Like Factor 6 Induces RNA Polymerase II Subunit RPB1 to Promote Kidney Injury.Journal of the American Society of Nephrology : JASN · 2025Article
- Renal tubular epithelial IGFBP7 interacts with PKM2 to drive renal lipid accumulation and fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Advances in Nano-Immunomodulatory Systems for the Treatment of Acute Kidney Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Kidney cell response to acute cardiorenal and isolated kidney ischemia-reperfusion injury.Physiological genomics · 2025Article
- Crosstalk between glomeruli and tubules.Nature reviews. Nephrology · 2025Review
- GALNT3 in Ischemia-Reperfusion Injury of the Kidney.Journal of the American Society of Nephrology : JASN · 2025Article
- Persistent subclinical renal injury in female rats following renal ischemia-reperfusion injury.Clinical science (London, England : 1979) · 2025Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Acute kidney injury (AKI) occurs in approximately 13% of hospitalized patients and predisposes patients to chronic kidney disease (CKD) through the AKI-to-CKD transition. Studies from our laboratory and others have demonstrated that maladaptive repair of proximal tubule cells (PTCs), including induction of dedifferentiation, G2/M cell cycle arrest, senescence, and profibrotic cytokine secretion, is a key process promoting AKI-to-CKD transition, kidney fibrosis, and CKD progression. The molecular mechanisms governing maladaptive repair and the relative contribution of dedifferentiation, G2/M arrest, and senescence to CKD remain to be resolved. We identified cyclin G1 (CG1) as a factor upregulated in chronically injured and maladaptively repaired PTCs. We demonstrated that global deletion of CG1 inhibits G2/M arrest and fibrosis. Pharmacological induction of G2/M arrest in CG1-knockout mice, however, did not fully reverse the antifibrotic phenotype. Knockout of CG1 did not alter dedifferentiation and proliferation in the adaptive repair response following AKI. Instead, CG1 specifically promoted the prolonged dedifferentiation of kidney tubule epithelial cells observed in CKD. Mechanistically, CG1 promotes dedifferentiation through activation of cyclin-dependent kinase 5 (CDK5). Deletion of CDK5 in kidney tubule cells did not prevent G2/M arrest but did inhibit dedifferentiation and fibrosis. Thus, CG1 and CDK5 represent a unique pathway that regulates maladaptive, but not adaptive, dedifferentiation, suggesting they could be therapeutic targets for CKD.
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