ArticleThe Journal of clinical investigation2004
Inhibition of diabetic nephropathy by a decoy peptide corresponding to the "handle" region for nonproteolytic activation of prorenin.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.
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Who cites it
146 citing papers in PubMed, 436 citations in OpenAlex.
- Elevated Prorenin Induces Podocyte Injury and Glomerular Fibrosis in cyp1a1-Prorenin Transgenic Rats.International journal of molecular sciences · 2026Article
- Association between adipose (pro)renin receptor expression and growth hormone deficiency in patients with non-functioning hypothalamic-pituitary masses.Journal of endocrinological investigation · 2026Article
- Renal tubular (pro)renin receptor deletion exacerbates kidney injury inAmerican journal of physiology. Renal physiology · 2025Article
- GLUT1 and prorenin receptor mediate differential regulation of TGF-β and CTGF in renal inner medullary collecting duct cells during high glucose conditions.Biological research · 2024Article
- RAAS in diabetic retinopathy: mechanisms and therapies.Archives of endocrinology and metabolism · 2024Review
- The Renin-Angiotensin System and Cardiovascular-Kidney-Metabolic Syndrome: Focus on Early-Life Programming.International journal of molecular sciences · 2024Review
- Cardiovascular effect of preeclampsia upon offspring development: Are (Pro) renin-renin receptor ((P)RR) and gender related?Iranian journal of basic medical sciences · 2024Article
- The (pro)renin receptor as a pharmacological target in cardiorenal diseaes.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Review
- The Renin Angiotensin System as a Therapeutic Target in Traumatic Brain Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- High-plasma soluble prorenin receptor is associated with vascular damage in male, but not female, mice fed a high-fat diet.American journal of physiology. Heart and circulatory physiology · 2023Article
- Module 4-Deficient CCN2/Connective Tissue Growth Factor Attenuates the Progression of Renal Fibrosis via Suppression of Focal Adhesion Kinase Phosphorylation in Tubular Epithelial Cells.Molecular and cellular biology · 2023Article
- The role of (pro)renin receptor and its soluble form in cardiovascular diseases.Frontiers in cardiovascular medicine · 2023Review
- Editorial: Insights in cardiovascular biologics and regenerative medicine: 2022.Frontiers in cardiovascular medicine · 2023Article
- Plasma and serum prorenin concentrations in diabetes, hypertension, and renal disease.Hypertension research : official journal of the Japanese Society of Hypertension · 2022Article
- Potential of soluble (pro)renin receptor in kidney disease: can it go beyond a biomarker?American journal of physiology. Renal physiology · 2022Review
- Endothelial cell polarity and extracellular matrix composition require functional ATP6AP2 during developmental and pathological angiogenesis.JCI insight · 2022Article
- Kidney Angiotensin in Cardiovascular Disease: Formation and Drug Targeting.Pharmacological reviews · 2022Review
- Effect of prorenin peptide vaccine on the early phase of diabetic retinopathy in a murine model of type 2 diabetes.PloS one · 2022Article
- Effect of Telmisartan and Quercetin in 5 Fluorouracil-Induced Renal Toxicity in Rats.Journal of inflammation research · 2022Article
- Blood Pressure Elevation of Tubular Specific (P)RR Transgenic Mice and Lethal Tubular Degeneration due to Possible Intracellular Interactions between (P)RR and Alternative Renin Products.International journal of molecular sciences · 2021Article
86 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
We found that when a site-specific binding protein interacts with the "handle" region of the prorenin prosegment, the prorenin molecule undergoes a conformational change to its enzymatically active state. This nonproteolytic activation is completely blocked by a decoy peptide with the handle region structure, which competitively binds to such a binding protein. Given increased plasma prorenin in diabetes, we examined the hypothesis that the nonproteolytic activation of prorenin plays a significant role in diabetic organ damage. Streptozotocin-induced diabetic rats were treated with subcutaneous administration of handle region peptide. Metabolic and renal histological changes and the renin-Ang system components in the plasma and kidneys were determined at 8, 16, and 24 weeks following streptozotocin treatment. Kidneys of diabetic rats contained increased Ang I and II without any changes in renin, Ang-converting enzyme, or angiotensinogen synthesis. Treatment with the handle region peptide decreased the renal content of Ang I and II, however, and completely inhibited the development of diabetic nephropathy without affecting hyperglycemia. We propose that the nonproteolytic activation of prorenin may be a significant mechanism of diabetic nephropathy. The mechanism and substances causing nonproteolytic activation of prorenin may serve as important therapeutic targets for the prevention of diabetic organ damage.
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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.