ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
Suppressing angiotensinogen synthesis attenuates kidney cyst formation in a Pkd1 mouse model.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 28 citations in OpenAlex.
- RNA-based therapeutic opportunities for the treatment of kidney diseases.Nature reviews. Nephrology · 2026Review
- New Approaches Targeting the Renin-Angiotensin System: Inhibition of Brain Aminopeptidase A, ACE2 Ubiquitination, and Angiotensinogen.The Canadian journal of cardiology · 2023Review
- Does the Naked Emperor Parable Apply to Current Perceptions of the Contribution of Renin Angiotensin System Inhibition in Hypertension?Current hypertension reports · 2022Review
- Serum bicarbonate is associated with kidney outcomes in autosomal dominant polycystic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2021Article
- Sequence variants in the renin-angiotensin system genes are associated with isolated multicystic dysplastic kidney in children.Pediatric research · 2021Article
- The Angiotensin-(1-12)/Chymase axis as an alternate component of the tissue renin angiotensin system.Molecular and cellular endocrinology · 2021Review
- Insights Into the Molecular Mechanisms of Polycystic Kidney Diseases.Frontiers in physiology · 2021Review
- Renal Ciliopathies: Sorting Out Therapeutic Approaches for Nephronophthisis.Frontiers in cell and developmental biology · 2021Review
- Metabolic Reprogramming and Reconstruction: Integration of Experimental and Computational Studies to Set the Path Forward in ADPKD.Frontiers in medicine · 2021Review
- STAT signaling in polycystic kidney disease.Cellular signalling · 2020Review
- Interferon Regulatory Factor-5 in Resident Macrophage Promotes Polycystic Kidney Disease.Kidney360 · 2020Article
- The pathogenic AGT c.856+1G>T mutation of a patient with multiple renal cysts and hypertension.Annals of translational medicine · 2019Article
- Salt-deficient diet exacerbates cystogenesis in ARPKD via epithelial sodium channel (ENaC).EBioMedicine · 2019Article
- Antisense oligonucleotides targeting angiotensinogen: insights from animal studies.Bioscience reports · 2019Review
- Emerging targeted strategies for the treatment of autosomal dominant polycystic kidney disease.Clinical kidney journal · 2018Review
- Attenuation of accelerated renal cystogenesis in Pkd1 mice by renin-angiotensin system blockade.American journal of physiology. Renal physiology · 2018Article
- Renin angiotensin aldosterone inhibition in the treatment of cardiovascular disease.Pharmacological research · 2017Review
- Heterotrimeric G protein signaling in polycystic kidney disease.Physiological genomics · 2016Review
- Structure and functions of angiotensinogen.Hypertension research : official journal of the Japanese Society of Hypertension · 2016Review
- Suppressing kidney angiotensinogen in blood pressure regulation.Physiological reports · 2016Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
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Abstract
Activation of the intrarenal renin angiotensin system (RAS) is believed to play an important role in the development of hypertension and cystogenesis in autosomal dominant polycystic kidney disease (ADPKD). Results of clinical studies testing RAS inhibitors in slowing the progression of cystic disease in ADPKD are inconclusive, and we hypothesized that current RAS inhibitors do not adequately suppress intrarenal RAS. For this study, we compared a novel Gen 2 antisense oligonucleotide (ASO) that inhibits angiotensinogen (Agt) synthesis to lisinopril in adult conditional Pkd1 systemic-knockout mice, a model of ADPKD. Six weeks after Pkd1 global gene knockout, the mice were treated with Agt-ASO (66 mg/kg/wk), lisinopril (100 mg/kg/d), PBS (control), or scrambled ASO (66 mg/kg/wk) for 10 wk, followed by tissue collection. Agt ASO resulted in significant reduction in plasma, liver, and kidney Agt, and increased kidney renin compared with control treatments. Kidneys from Agt-ASO-treated mice were not as enlarged and showed reduced cystic volume compared with lisinopril or control treatments. Blood pressure was better controlled with lisinopril than with Agt-ASO. Agt-ASO suppressed cell proliferation in both cystic and noncystic cells compared with lisinopril and control treatments. However, Agt-ASO did not reduce cell proliferation in liver, which indicates that Agt-ASO targets cell signaling pathways that specifically suppresses cystogenesis in the kidney. These data suggest that Agt-ASO effectively attenuates intrarenal RAS and therefore can be a novel and effective agent for treating ADPKD.
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