ArticleJCI insight2018
Krüppel-like factor 4 is a negative regulator of STAT3-induced glomerular epithelial cell proliferation.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 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.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Functional characterization of podocyte-expressed THSD7A in experimental membranous nephropathy.JCI insight · 2026Article
- Application of the nephrotoxic serum nephritis model in glomerulonephritis research.Molecular medicine (Cambridge, Mass.) · 2026Review
- Podocyte-Specific Deletion of STAT3 in Krüppel-Like Factor 4-Related Experimental Podocytopathy.Journal of the American Society of Nephrology : JASN · 2026Article
- Signal Transducer and Activator of Transcription 3 in the Podocyte: A Key Mediator of Podocyte-Parietal Epithelial Cell Cross-Talk and Glomerular Health?Journal of the American Society of Nephrology : JASN · 2026Article
- Knock-down of the long isoform of the WNK1 kinase mitigates the anti-glomerular basement membrane glomerulonephritis in mice.Scientific reports · 2026Article
- Targeting STAT3 in systemic lupus erythematosus and lupus nephritis: mechanisms, therapeutic advances, and structure-informed perspectives.Frontiers in pharmacology · 2026Review
- Article
- Regulatory Role of Zinc in Acute Promyelocytic Leukemia: Cellular and Molecular Aspects with Therapeutic Implications.International journal of molecular sciences · 2025Review
- The Life of a Kidney Podocyte.Acta physiologica (Oxford, England) · 2025Review
- Diagnostic value of the correlation between urinary MDM2 and podocyte mitotic catastrophe in diabetic kidney disease.Diabetology & metabolic syndrome · 2025Article
- Cell cycle disorders in podocytes: an emerging and increasingly recognized phenomenon.Cell death discovery · 2025Review
- Piezo1, F-Actin Remodeling, and Podocyte Survival and Regeneration.Journal of the American Society of Nephrology : JASN · 2025Article
- Hyperactivation of p53 contributes to mitotic catastrophe in podocytes through regulation of the Wee1/CDK1/cyclin B1 axis.Renal failure · 2024Article
- A Small Molecule Agonist of Krüppel-Like Factor 15 in Proteinuric Kidney Disease.Journal of the American Society of Nephrology : JASN · 2024Article
- STAT3 blockade ameliorates LPS-induced kidney injury through macrophage-driven inflammation.Cell communication and signaling : CCS · 2024Article
- STAT3 Protein-Protein Interaction Analysis Finds P300 as a Regulator of STAT3 and Histone 3 Lysine 27 Acetylation in Pericytes.Biomedicines · 2024Article
- Central role of podocytes in mediating cellular cross talk in glomerular health and disease.American journal of physiology. Renal physiology · 2024Review
- Transcriptional state dynamics lead to heterogeneity and adaptive tumor evolution in urothelial bladder carcinoma.Communications biology · 2023Article
- The loss of profilin1 is catastrophic to podocytes.The Journal of clinical investigation · 2023Article
- Signaling pathways of chronic kidney diseases, implications for therapeutics.Signal transduction and targeted therapy · 2022Review
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 1 country.
Funding
Abstract
Pathologic glomerular epithelial cell (GEC) hyperplasia is characteristic of both rapidly progressive glomerulonephritis (RPGN) and subtypes of focal segmental glomerulosclerosis (FSGS). Although initial podocyte injury resulting in activation of STAT3 signals GEC proliferation in both diseases, mechanisms regulating this are unknown. Here, we show that the loss of Krüppel-like factor 4 (KLF4), a zinc-finger transcription factor, enhances GEC proliferation in both RPGN and FSGS due to dysregulated STAT3 signaling. We observed that podocyte-specific knockdown of Klf4 (C57BL/6J) increased STAT3 signaling and exacerbated crescent formation after nephrotoxic serum treatment. Interestingly, podocyte-specific knockdown of Klf4 in the FVB/N background alone was sufficient to activate STAT3 signaling, resulting in FSGS with extracapillary proliferation, as well as renal failure and reduced survival. In cultured podocytes, loss of KLF4 resulted in STAT3 activation and cell-cycle reentry, leading to mitotic catastrophe. This triggered IL-6 release into the supernatant, which activated STAT3 signaling in parietal epithelial cells. Conversely, either restoration of KLF4 expression or inhibition of STAT3 signaling improved survival in KLF4-knockdown podocytes. Finally, human kidney biopsy specimens with RPGN exhibited reduced KLF4 expression with a concomitant increase in phospho-STAT3 expression as compared with controls. Collectively, these results suggest the essential role of KLF4/STAT3 signaling in podocyte injury and its regulation of aberrant GEC proliferation.
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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.