ArticlePloS one2019
Tyrphostin AG490 reduces inflammation and fibrosis in neonatal obstructive nephropathy.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Inhibition of IL-6/STAT3 Signaling by N-Trans-Hibiscusamide and Its Derivative in a Mouse Model of Collagen-Induced Arthritis.Food science & nutrition · 2026Article
- Pancreatic Elastase Affects Liver Injury by Activating Proinflammatory Cytokines in Kupffer Cells via the JAK2/STAT3 Signaling Pathway.Current molecular medicine · 2026Article
- Single-Cell RNA Sequencing Delineates Renal Anti-Fibrotic Mechanisms Mediated by TRPC6 Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Luteolin Alleviates Ulcerative Colitis in Mice by Modulating Gut Microbiota and Plasma Metabolism.Nutrients · 2025Article
- Interleukin-10 enhances recruitment of immune cells in the neonatal mouse model of obstructive nephropathy.Scientific reports · 2024Article
- Research progress on the mechanism of renal interstitial fibrosis in obstructive nephropathy.Heliyon · 2023Review
- TLR2 mediates renal apoptosis in neonatal mice subjected experimentally to obstructive nephropathy.PloS one · 2023Article
- Cyanidin-3-O-glucoside plays a protective role against renal ischemia/ reperfusion injury via the JAK/STAT pathway.Acta cirurgica brasileira · 2023Article
- Signaling pathways of chronic kidney diseases, implications for therapeutics.Signal transduction and targeted therapy · 2022Review
- Phosphorylated STAT3 suppresses microRNA-19b/1281 to aggravate lung injury in mice with type 2 diabetes mellitus-associated pulmonary tuberculosis.Journal of cellular and molecular medicine · 2020Article
- Renal developmental genes are differentially regulated after unilateral ureteral obstruction in neonatal and adult mice.Scientific reports · 2020Article
- Extratubular Polymerized Uromodulin Induces Leukocyte Recruitment and InflammationFrontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCongenital obstructive nephropathy is the main cause of end-stage renal disease in infants and children. Renal insufficiency is due to impaired growth and maturation in the developing kidney with obstruction. Congenital obstructive nephropathy leads to cytokine mediated inflammation and the development of interstitial fibrosis. The Janus kinase-2 (JAK-2) and Signal Transducer and Activator of Transcription'-3 (STAT3) are involved in cytokine production, inflammation, and interstitial fibrosis.
methodsWe studied the role of JAK2/STAT3 in a model of congenital obstructive nephropathy using unilateral ureteral obstruction (UUO) in neonatal mice at the second day of life. Cytokine production, inflammation, and interstitial fibrosis were analyzed in obstructed and sham operated kidneys of neonatal mice treated with or without JAK2/STAT3 inhibitor Tyrphostin AG490. To mimic obstruction and distension, proximal tubular cells were stretched in vitro.
resultsWe show that STAT3 is highly activated in the developing kidney with obstruction and in proximal tubular cells following stretch. JAK2/STAT3 activation mediates cytokine release and leukocyte recruitment into neonatal kidneys after UUO. Pharmacological blockade of JAK2/STAT3 by Tyrphostin AG490 reduced inflammation, tubular apoptosis, and interstitial fibrosis. JAK2/STAT3 blockade decreased pro-inflammatory and profibrotic mediators in tubular cells.
conclusionOur findings provide evidence that JAK2/STAT3 mediates inflammation and fibrosis in the developing kidney with obstruction. Blocking JAK2/STAT3 may prove beneficial in congenital obstructive nephropathy in children.
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