ArticlePloS one2013
Angiotensin II type 1 receptor antagonist attenuates lacrimal gland, lung, and liver fibrosis in a murine model of chronic graft-versus-host disease.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Ocular graft-versus-host disease after hematopoietic cell transplantation: Expert review from the Late Effects and Quality of Life Working Committee of the CIBMTR and Transplant Complications Working Party of the EBMT.Bone marrow transplantation · 2019Pooled it
- Trial
- Exploratory study on the efficacy of topical pan-JAK inhibitor in ocular and skin GVHD in a sclerodermatous GVHD mouse model.Scientific reports · 2025Article
- Evolving therapeutic paradigms in ocular graft-versus-host disease.Eye (London, England) · 2024Article
- The Necroptosis Pathway Is Upregulated in the Cornea in Mice With Ocular Graft-Versus-Host Disease.Investigative ophthalmology & visual science · 2024Article
- A Novel Murine Model for Lupus-Like Ocular Chronic Graft-Versus-Host Disease.Investigative ophthalmology & visual science · 2024Article
- Activation of SIRT1/Nrf2/HO-1 and Beclin-1/AMPK/mTOR autophagy pathways by eprosartan ameliorates testicular dysfunction induced by testicular torsion in rats.Scientific reports · 2024Article
- Murine models of graft versus host disease (GVHD): Focus on ocular GVHD.The ocular surface · 2023Review
- Endothelial Injury Syndromes after Allogeneic Hematopoietic Stem Cell Transplantation: Angiopetin-2 as a Novel Predictor of the Outcome and the Role of Functional Autoantibodies against Angiotensin II Type 1 and Endothelin A Receptor.International journal of molecular sciences · 2023Article
- Recent advances in ocular graft-versus-host disease.Frontiers in immunology · 2023Review
- Autoimmune Epithelitis and Chronic Inflammation in Sjögren's Syndrome-Related Dry Eye Disease.International journal of molecular sciences · 2021Review
- Local Renin-Angiotensin System Activation and Myofibroblast Formation in Graft Versus Host Disease-Associated Conjunctival Fibrosis.Investigative ophthalmology & visual science · 2021Article
- National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: IV. The 2020 Highly morbid forms report.Transplantation and cellular therapy · 2021Article
- Observation of Chronic Graft-Versus-Host Disease Mouse Model Cornea with In Vivo Confocal Microscopy.Diagnostics (Basel, Switzerland) · 2021Article
- Cascade of Inflammatory, Fibrotic Processes, and Stress-Induced Senescence in Chronic GVHD-Related Dry Eye Disease.International journal of molecular sciences · 2021Review
- The Potential Association between the Risk of Post-Surgical Adhesion and the Activated Local Angiotensin II Type 1 Receptors: Need for Novel Treatment Strategies.Gastrointestinal tumors · 2021Review
- Positive Effects of Oral Antibiotic Administration in Murine Chronic Graft-Versus-Host Disease.International journal of molecular sciences · 2021Article
- AT1R Activating Autoantibodies in Hematopoietic Stem Cell Transplantation.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2020Article
- Receptor-Associated Prorenin System in the Trabecular Meshwork of Patients with Primary Open-Angle Glaucoma and Neovascular Glaucoma.Journal of clinical medicine · 2020Article
- Ocular Graft-versus-Host Disease after Hematopoietic Cell Transplantation: Expert Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2019Review
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic graft-versus-host disease (cGVHD), a serious complication following allogeneic HSCT (hematopoietic stem cell transplantation), is characterized by systemic fibrosis. The tissue renin-angiotensin system (RAS) is involved in the fibrotic pathogenesis, and an angiotensin II type 1 receptor (AT1R) antagonist can attenuate fibrosis. Tissue RAS is present in the lacrimal gland, lung, and liver, and is known to be involved in the fibrotic pathogenesis of the lung and liver. This study aimed to determine whether RAS is involved in fibrotic pathogenesis in the lacrimal gland and to assess the effect of an AT1R antagonist on preventing lacrimal gland, lung, and liver fibrosis in cGVHD model mice. We used the B10.D2→BALB/c (H-2(d)) MHC-compatible, multiple minor histocompatibility antigen-mismatched model, which reflects clinical and pathological symptoms of human cGVHD. First, we examined the localization and expression of RAS components in the lacrimal glands using immunohistochemistry and quantitative real-time polymerase chain reaction (PCR). Next, we administered an AT1R antagonist (valsartan; 10 mg/kg) or angiotensin II type 2 receptor (AT2R) antagonist (PD123319; 10 mg/kg) intraperitoneally into cGVHD model mice and assessed the fibrotic change in the lacrimal gland, lung, and liver. We demonstrated that fibroblasts expressed angiotensin II, AT1R, and AT2R, and that the mRNA expression of angiotensinogen was greater in the lacrimal glands of cGVHD model mice than in controls generated by syngeneic-HSCT. The inhibition experiment revealed that fibrosis of the lacrimal gland, lung, and liver was suppressed in mice treated with the AT1R antagonist, but not the AT2R antagonist. We conclude that RAS is involved in fibrotic pathogenesis in the lacrimal gland and that AT1R antagonist has a therapeutic effect on lacrimal gland, lung, and liver fibrosis in cGVHD model mice. Our findings point to AT1R antagonist as a possible target for therapeutic intervention in cGVHD.
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