ArticleKidney international2016
Ligand trap for the activin type IIA receptor protects against vascular disease and renal fibrosis in mice with chronic kidney disease.
Article in Kidney international, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 79 citations in OpenAlex.
- Mineral and Bone Disease in CKD and Kidney Transplantation: Controversies, Gaps, and a Path Forward.Kidney international reports · 2026Review
- Smad2/3 Signaling Mediates the Atrophic Response in Vocal Fold Myoblasts In Vitro.The Laryngoscope · 2026Article
- Integrative Proteome- and Phenome-Wide Assessment Uncovers Causal Protein Drivers and Drug Targets for Heterogeneous Kidney Diseases.medRxiv : the preprint server for health sciences · 2025Article
- Molecular pathophysiology of chronic kidney disease-mineral and bone disorder: Focus on the fibroblast growth factor 23-Klotho axis and bone turnover dynamics.Experimental physiology · 2025Review
- Development of animal models with chronic kidney disease-mineral and bone disorder based on clinical characteristics and pathogenesis.Frontiers in endocrinology · 2025Review
- The Potential Role of Cardiokines in Heart and Kidney Diseases.Current medicinal chemistry · 2025Review
- Does the Composition of Gut Microbiota Affect Chronic Kidney Disease? Molecular Mechanisms Contributed to Decreasing Glomerular Filtration Rate.International journal of molecular sciences · 2024Review
- Activin A: a marker of mineral bone disorder in children with chronic kidney disease?Pediatric nephrology (Berlin, Germany) · 2024Article
- In chronic kidney disease altered cardiac metabolism precedes cardiac hypertrophy.American journal of physiology. Renal physiology · 2024Article
- Advances in sarcopenia: mechanisms, therapeutic targets, and intervention strategies.Archives of pharmacal research · 2024Review
- Plasma activin A rises with declining kidney function and is independently associated with mortality in patients with chronic kidney disease.Clinical kidney journal · 2023Article
- Trunk muscle quality and quantity are associated with renal volume in nondiabetic people.Clinical kidney journal · 2023Article
- The WNT/β-catenin system in chronic kidney disease-mineral bone disorder syndrome.International urology and nephrology · 2023Review
- Diminished vasculogenesis under inflammatory conditions is mediated by Activin A.Angiogenesis · 2023Article
- Pyroptosis in renal inflammation and fibrosis: current knowledge and clinical significance.Cell death & disease · 2023Review
- Pathophysiology of bone disease in chronic kidney disease: from basics to renal osteodystrophy and osteoporosis.Frontiers in physiology · 2023Review
- The Growth Factors: Potential Biomarkers and Therapeutic Targets in Kidney Diseases.Kidney diseases (Basel, Switzerland) · 2022Review
- The Calcified Vasculature in Chronic Kidney Disease Secretes Factors that Inhibit Bone Mineralization.JBMR plus · 2022Article
- Urinary Activin A: A Novel Biomarker for Human Acute Kidney Injury.Diagnostics (Basel, Switzerland) · 2022Article
- New Insights to the Crosstalk between Vascular and Bone Tissue in Chronic Kidney Disease-Mineral and Bone Disorder.Metabolites · 2021Review
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5 authors at 2 institutions in 1 country.
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Abstract
The causes of cardiovascular mortality associated with chronic kidney disease (CKD) are partly attributed to the CKD-mineral bone disorder (CKD-MBD). The causes of the early CKD-MBD are not well known. Our discovery of Wnt (portmanteau of wingless and int) inhibitors, especially Dickkopf 1, produced during renal repair as participating in the pathogenesis of the vascular and skeletal components of the CKD-MBD implied that additional pathogenic factors are critical. In the search for such factors, we studied the effects of activin receptor type IIA (ActRIIA) signaling by using a ligand trap for the receptor, RAP-011 (a soluble extracellular domain of ActRIIA fused to a murine IgG-Fc fragment). In a mouse model of CKD that stimulated atherosclerotic calcification, RAP-011 significantly increased aortic ActRIIA signaling assessed by the levels of phosphorylated Smad2/3. Furthermore, RAP-011 treatment significantly reversed CKD-induced vascular smooth muscle dedifferentiation as assessed by smooth muscle 22α levels, osteoblastic transition, and neointimal plaque calcification. In the diseased kidneys, RAP-011 significantly stimulated αklotho levels and it inhibited ActRIIA signaling and decreased renal fibrosis and proteinuria. RAP-011 treatment significantly decreased both renal and circulating Dickkopf 1 levels, showing that Wnt activation was downstream of ActRIIA. Thus, ActRIIA signaling in CKD contributes to the CKD-MBD and renal fibrosis. ActRIIA signaling may be a potential therapeutic target in CKD.
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