ArticleFrontiers in immunology2021
Pharmacological Inhibition of STAT6 Ameliorates Myeloid Fibroblast Activation and Alternative Macrophage Polarization in Renal Fibrosis.
Article in Frontiers in immunology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 70 citations in OpenAlex.
- KLF transcription factors in metabolic kidney disease: from podocyte protection to tubulointerstitial fibrosis.International urology and nephrology · 2026Review
- OLFM4 mediating ischemia/reperfusion-induced kidney injury by regulating renal tubular epithelial cells ferroptosis via GPX4.Molecular biology reports · 2026Article
- Spatiotemporal Control of Intercellular Crosstalk: A New Therapeutic Paradigm for Halting Acute Kidney Injury to Chronic Kidney Disease Transition.Biomolecules · 2026Review
- Apoptotic extracellular vesicles derived from MSCs exposed to hypoxic and inflammatory environments slow intervertebral disc degeneration by enhancing cell activity and regulating immunity microenvironment.Materials today. Bio · 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
- Phosphodiesterase 5 Inhibitor Improves Insulin Sensitivity by Regulating Adipose Tissue Macrophage Polarization in Diet-Induced Obese Mice.Diabetes & metabolism journal · 2026Article
- Critical role of transcription factor SOX4 in tubular epithelial cell dedifferentiation and fibroblast activation during kidney fibrosis.Kidney international · 2026Article
- Kidney angiopoietin-like protein 4 regulates fibrotic responses in diabetic kidney disease.Frontiers in pharmacology · 2026Review
- Targeting DPP9 attenuates podocyte injury by regulating NRF2 antioxidant signaling.Frontiers in pharmacology · 2026Article
- Cell-state- and compartment-dependent PI3K/Akt redox signaling in chronic kidney disease: mechanisms and translational implications.Frontiers in pharmacology · 2026Review
- 15- Deoxy-Δ12,14-prostaglandin J2 upregulates COX-2 expression and PGEFrontiers in pharmacology · 2026Article
- Weekly administration of betulinic acid prevents development of chronic renal failure from acute renal failure in folic acid-induced mouse model of kidney injury.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- The crucial role of metabolic reprogramming in driving macrophage conversion in kidney disease.Cellular & molecular biology letters · 2025Review
- The multifaceted role of macrophages in kidney physiology and diseases.Frontiers in immunology · 2025Review
- The Role of Ursodeoxycholic Acid Administration During the COVID-19 Pandemic: A Questionnaire Survey.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2025Article
- Harnessing the multi-targeted potential of rehmanniae radix natural products against renal fibrosis: a mechanistic review.Frontiers in pharmacology · 2025Review
- Bioinformatics-based analysis and experimental validation of PANoptosis-related biomarkers and immune infiltration in diabetic nephropathy.Frontiers in endocrinology · 2025Article
- Renoprotective effects of GHRH agonist MR409 is associated with reduced oxidative stress and ferroptosis in diabetic mice.Frontiers in pharmacology · 2025Article
- Huangkui capsule combined with finerenone attenuates diabetic nephropathy by regulating the JAK2/STAT3 signaling pathway based on network pharmacology, molecular docking, and experimental verification.Frontiers in pharmacology · 2025Article
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Authors and funding
7 authors at 1 institution in 1 country.
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Abstract
A hallmark of chronic kidney disease is renal fibrosis, which can result in progressive loss of kidney function. Currently, there is no effective therapy for renal fibrosis. Therefore, there is an urgent need to identify potential drug targets for renal fibrosis. In this study, we examined the effect of a selective STAT6 inhibitor, AS1517499, on myeloid fibroblast activation, macrophage polarization, and development of renal fibrosis in two experimental murine models. To investigate the effect of STAT6 inhibition on myeloid fibroblast activation, macrophage polarization, and kidney fibrosis, wild-type mice were subjected to unilateral ureteral obstruction or folic acid administration and treated with AS1517499. Mice treated with vehicle were used as control. At the end of experiments, kidneys were harvested for analysis of myeloid fibroblast activation, macrophage polarization, and renal fibrosis and function. Unilateral ureteral obstruction or folic acid administration induced STAT6 activation in interstitial cells of the kidney, which was significantly abolished by AS1517499 treatment. Mice treated with AS1517499 accumulated fewer myeloid fibroblasts and myofibroblasts in the kidney with ureteral obstruction or folic acid nephropathy compared with vehicle-treated mice. Moreover, AS1517499 significantly suppressed M2 macrophage polarization in the injured kidney. Furthermore, AS1517499 markedly reduced the expression levels of extracellular matrix proteins, and development of kidney fibrosis and dysfunction. These findings suggest that AS1517499 inhibits STAT6 activation, suppresses myeloid fibroblast activation, reduces M2 macrophage polarization, attenuates extracellular matrix protein production, and preserves kidney function. Therefore, targeting STAT6 with AS1517499 is a novel therapeutic approach for chronic kidney disease.
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