ArticleJournal of the American Society of Nephrology : JASN2015
JAK3/STAT6 Stimulates Bone Marrow-Derived Fibroblast Activation in Renal Fibrosis.
Article in Journal of the American Society of Nephrology : JASN, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.
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Who cites it
75 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Crosstalk between fibroblasts and immunocytes in fibrosis: From molecular mechanisms to clinical trials.Clinical and translational medicine · 2024Pooled it
- Macrophage-to-Myofibroblast Transdifferentiation Contributes to Pulmonary Fibrosis via the MERTK-SPP1-SRC-TKS5 Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Piezo1 promote macrophage-to-myofibroblast transition and bladder fibrosis in neurogenic bladder.World journal of urology · 2026Article
- Kat5 deficiency in alveolar type II cells licenses STAT6-driven glycolytic reprogramming and pulmonary fibrosis.Nature communications · 2026Article
- Induction of fibrosis in human kidney organoids delineates mechanisms and therapeutic targets of fibrotic kidney disease.Stem cell research & therapy · 2026Article
- TNFAIP6, an independent prognostic monitor and therapy target, promoted low-grade glioma recurrence and progression via JAK3-STAT6 signaling.International journal of surgery (London, England) · 2026Article
- Macrophage RNA polymerase II subunit 5-mediating protein deficiency exacerbates kidney inflammation and fibrosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- The role of interleukin-4 in acute kidney injury and chronic kidney disease: a literature review.BMC nephrology · 2026Review
- From bench to bedside: adipose tissue fibrosis in obesity, anti-diabetic therapies, and bariatric surgery.The Korean journal of internal medicine · 2026Review
- Circulating Fibrocytes: Cellular Mediators of Tissue Fibrosis.International journal of molecular sciences · 2026Review
- Spatial transcriptomics reveals injury-responsive compartments and coordinated immune-fibrotic signaling in ANCA-associated renal vasculitis.Frontiers in immunology · 2026Article
- Renal allograft interstitial fibrosis: multicellular interactions and therapeutic strategies.Frontiers in immunology · 2026Review
- Single Cell and Spatial Transcriptomics Define a Proinflammatory and Profibrotic Niche After Kidney Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Tracing the origin of myofibroblasts in kidney fibrosis.Nature communications · 2025Article
- Therapeutic potential of Janus kinase inhibitors for the management of fibrosis in inflammatory bowel disease.Journal of Crohn's & colitis · 2025Review
- Senescent renal tubular cells derived extracellular vesicles transported miR-20a and miR-21 induced macrophage-to-myofibroblast transition in renal fibrosis after ischemia reperfusion injury.International journal of biological sciences · 2025Article
- Mechanisms Underlying the Impact of Interleukin Family on Acute Kidney Injury: Pathogenesis, Progression, and Therapy.Research (Washington, D.C.) · 2025Review
- [Tofacitinib inhibits the transformation of lung fibroblasts into myofibroblasts through JAK/STAT3 pathway].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2024Article
- Kidney Aging and Chronic Kidney Disease.International journal of molecular sciences · 2024Review
- Targeting Macrophages: Therapeutic Approaches in Diabetic Kidney Disease.International journal of molecular sciences · 2024Review
15 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Renal fibrosis is a final common manifestation of CKD resulting in progressive loss of kidney function. Bone marrow-derived fibroblast precursors contribute significantly to the pathogenesis of renal fibrosis. However, the signaling mechanisms underlying the activation of bone marrow-derived fibroblast precursors in the kidney are not fully understood. In this study, we investigated the role of the Janus kinase 3 (JAK3)/signal transducer and activator of transcription (STAT6) signaling pathway in the activation of bone marrow-derived fibroblasts. In cultured mouse monocytes, IL-4 or IL-13 activated STAT6 and induced expression of α-smooth muscle actin and extracellular matrix proteins (fibronectin and collagen I), which was abolished by a JAK3 inhibitor (CP690,550) in a dose-dependent manner or blocked in the absence of STAT6. In vivo, STAT6 was activated in interstitial cells of the obstructed kidney, an effect that was abolished by CP690,550. Mice treated with CP690,550 accumulated fewer bone marrow-derived fibroblasts in the obstructed kidneys compared with vehicle-treated mice. Treatment with CP690,550 also significantly reduced myofibroblast transformation, matrix protein expression, fibrosis development, and apoptosis in obstructed kidneys. Furthermore, STAT6-deficient mice accumulated fewer bone marrow-derived fibroblasts in the obstructed kidneys, produced less extracellular matrix protein, and developed much less fibrosis. Finally, wild-type mice engrafted with STAT6(-/-) bone marrow cells displayed fewer bone marrow-derived fibroblasts in the obstructed kidneys and showed less severe renal fibrosis compared with wild-type mice engrafted with STAT6(+/+) bone marrow cells. Our results demonstrate that JAK3/STAT6 has an important role in bone marrow-derived fibroblast activation, extracellular matrix production, and interstitial fibrosis development.
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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 OpenQuestion graph.