ArticleProceedings of the National Academy of Sciences of the United States of America2011
Signal transducer and activator of transcription-6 (STAT6) inhibition suppresses renal cyst growth in polycystic kidney disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. 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, 79 citations in OpenAlex.
- Cytokine-Driven Janus Kinase Signal Transducer and Activator of Transcription Pathway Hyperactivity Predicts Disease Severity in Pediatric FSGS.Kidney360 · 2026Article
- Development of a cyst-targeted therapy for polycystic kidney disease using an antagonistic dimeric IgA monoclonal antibody against cMET.Cell reports. Medicine · 2025Article
- Advances and Challenges in Modeling Autosomal Dominant Polycystic Kidney Disease: A Focus on Kidney Organoids.Biomedicines · 2025Review
- Sex-specific molecular signature of mouse podocytes in homeostasis and in response to pharmacological challenge with rapamycin.Biology of sex differences · 2024Article
- Wall Tension and Tubular Resistance in Kidney Cystic Conditions.Biomedicines · 2023Review
- Crosstalk between the mTOR pathway and primary cilia in human diseases.Current topics in developmental biology · 2023Review
- Effects of Suramin on Polycystic Kidney Disease in a Mouse Model of Polycystin-1 Deficiency.International journal of molecular sciences · 2022Article
- STAT6 contributes to renal fibrosis by modulating PPARα-mediated tubular fatty acid oxidation.Cell death & disease · 2022Article
- Ppia is the most stable housekeeping gene for qRT-PCR normalization in kidneys of three Pkd1-deficient mouse models.Scientific reports · 2021Article
- Retarding Progression of Chronic Kidney Disease in Autosomal Dominant Polycystic Kidney Disease with Metformin and Other Therapies: An Update of New Insights.International journal of general medicine · 2021Review
- STAT signaling in polycystic kidney disease.Cellular signalling · 2020Review
- Review
- Signaling through the interleukin-4 and interleukin-13 receptor complexes regulates cholangiocyte TMEM16A expression and biliary secretion.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Epigenetics and cell cycle regulation in cystogenesis.Cellular signalling · 2020Review
- Rationale and Roadmap for Developing Panels of Hotspot Cancer Driver Gene Mutations as Biomarkers of Cancer Risk.Environmental and molecular mutagenesis · 2020Review
- Polycystin-1 affects cancer cell behaviour and interacts with mTOR and Jak signalling pathways in cancer cell lines.Journal of cellular and molecular medicine · 2019Article
- Renal expression of JAK2 is high in polycystic kidney disease and its inhibition reduces cystogenesis.Scientific reports · 2019Article
- Emerging targeted strategies for the treatment of autosomal dominant polycystic kidney disease.Clinical kidney journal · 2018Review
- Are Cyst-Associated Macrophages in Polycystic Kidney Disease the Equivalent to TAMs in Cancer?Journal of the American Society of Nephrology : JASN · 2018Article
- Identification of targets of IL-13 and STAT6 signaling in polycystic kidney disease.American journal of physiology. Renal physiology · 2018Article
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Autosomal-dominant (AD) polycystic kidney disease (PKD) is a leading cause of renal failure in the United States, and currently lacks available treatment options to slow disease progression. Mutations in the gene coding for polycystin-1 (PC1) underlie the majority of cases but the function of PC1 has remained poorly understood. We have previously shown that PC1 regulates the transcriptional activity of signal transducer and activator of transcription-6 (STAT6). Here we show that STAT6 is aberrantly activated in cyst-lining cells in PKD mouse models. Activation of the STAT6 pathway leads to a positive feedback loop involving auto/paracrine signaling by IL13 and the IL4/13 receptor. The presence of IL13 in cyst fluid and the overexpression of IL4/13 receptor chains suggests a mechanism of sustained STAT6 activation in cysts. Genetic inactivation of STAT6 in a PKD mouse model leads to significant inhibition of proliferation and cyst growth and preservation of renal function. We show that the active metabolite of leflunomide, a drug approved for treatment of arthritis, inhibits STAT6 in renal epithelial cells. Treatment of PKD mice with this drug leads to amelioration of the renal cystic disease similar to genetic STAT6 inactivation. These results suggest STAT6 as a promising drug target for treatment of ADPKD.
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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.