ArticleCell death & disease2021
Permissive effect of GSK3β on profibrogenic plasticity of renal tubular cells in progressive chronic kidney disease.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 44 citations in OpenAlex.
- Ligustroflavone alleviates chronic kidney disease by inhibiting ferroptosis through the GSK3β/NRF2 signaling pathway.Redox report : communications in free radical research · 2026Article
- The E3 ubiquitin ligase Itch plays an essential role in kidney fibrosis by inhibiting Dvl2/GSK3β/β-catenin signaling pathway.Cell death and differentiation · 2026Article
- Hypertension-Induced Renal Injury: From Pathophysiology to Therapeutic Perspectives.Biomedicines · 2026Review
- Taohong Siwu Decoction relieves renal fibrosis: based on network pharmacology and experimental confirmation.Renal failure · 2025Article
- Exploring the common genetic basis of metabolic syndrome-related diseases and chronic kidney disease: insights from extensive genome-wide cross-trait analyses.BioData mining · 2025Article
- Decoy Receptor 2 as a Cell Cycle Arrest Biomarker for Predicting Renal Recovery Following Acute Kidney Injury.Journal of cellular and molecular medicine · 2025Article
- Glycogen synthase kinase 3β: a key player in progressive chronic kidney disease.Clinical science (London, England : 1979) · 2025Review
- Mineralocorticoid receptor antagonism attenuates arteriovenous fistula stenosis by modulating the phenotype of vascular smooth muscle cells.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025Article
- Modulation of TGF-β signaling new approaches toward kidney disease and fibrosis therapy.International journal of biological sciences · 2025Review
- RTN1A mediates diabetes-induced AKI-to-CKD transition.JCI insight · 2024Article
- Article
- LATS2 degradation promoted fibrosis damage and rescued by vitamin K3 in lupus nephritis.Arthritis research & therapy · 2024Article
- Treatment for type 2 diabetes and diabetic nephropathy by targeting Smad3 signaling.International journal of biological sciences · 2024Article
- Pathway from Acute Kidney Injury to Chronic Kidney Disease: Molecules Involved in Renal Fibrosis.International journal of molecular sciences · 2023Review
- Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway.Cell death & disease · 2023Article
- Six Decades of History of Hypertension Research at the University of Toledo: Highlighting Pioneering Contributions in Biochemistry, Genetics, and Host-Microbiota Interactions.Current hypertension reports · 2022Review
- Age-related GSK3β overexpression drives podocyte senescence and glomerular aging.The Journal of clinical investigation · 2022Article
- GSK3β-dependent lysosome biogenesis: An effective pathway to mitigate renal fibrosis with LM49.Frontiers in pharmacology · 2022Article
- Smad3 Signatures in Renal Inflammation and Fibrosis.International journal of biological sciences · 2022Review
- A Deep Insight Into Regulatory T Cell Metabolism in Renal Disease: Facts and Perspectives.Frontiers in immunology · 2022Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Renal tubular epithelial cells (TECs) play a key role in renal fibrogenesis. After persistent injuries that are beyond self-healing capacity, TECs will dedifferentiate, undergo growth arrest, convert to profibrogenic phenotypes, and resort to maladaptive plasticity that ultimately results in renal fibrosis. Evidence suggests that glycogen synthase kinase (GSK) 3β is centrally implicated in kidney injury. However, its role in renal fibrogenesis is obscure. Analysis of publicly available kidney transcriptome database demonstrated that patients with progressive chronic kidney disease (CKD) exhibited GSK3β overexpression in renal tubulointerstitium, in which the predefined hallmark gene sets implicated in fibrogenesis were remarkably enriched. In vitro, TGF-β1 treatment augmented GSK3β expression in TECs, concomitant with dedifferentiation, cell cycle arrest at G2/M phase, excessive accumulation of extracellular matrix, and overproduction of profibrotic cytokines like PAI-1 and CTGF. All these profibrogenic phenotypes were largely abrogated by GSK3β inhibitors or by ectopic expression of a dominant-negative mutant of GSK3β but reinforced in cells expressing the constitutively active mutant of GSK3β. Mechanistically, GSK3β suppressed, whereas inhibiting GSK3β facilitated, the activity of cAMP response element-binding protein (CREB), which competes for CREB-binding protein, a transcriptional coactivator essential for TGF-β1/Smad signaling pathway to drive TECs profibrogenic plasticity. In vivo, in mice with folic acid-induced progressive CKD, targeting of GSK3β in renal tubules via genetic ablation or by microdose lithium mitigated the profibrogenic plasticity of TEC, concomitant with attenuated interstitial fibrosis and tubular atrophy. Collectively, GSK3β is likely a pragmatic therapeutic target for averting profibrogenic plasticity of TECs and improving renal fibrosis.
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