ArticleHypertension research : official journal of the Japanese Society of Hypertension2010
Glomerular angiotensinogen is induced in mesangial cells in diabetic rats via reactive oxygen species--ERK/JNK pathways.
Article in Hypertension research : official journal of the Japanese Society of Hypertension, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 61 citations in OpenAlex.
- Isoflavones Inhibit Hydrogen Peroxide-Induced Angiotensinogen Secretion.International journal of molecular sciences · 2025Article
- Hepatic and proximal tubule angiotensinogen play distinct roles in kidney dysfunction, glomerular and tubular injury, and fibrosis progression.American journal of physiology. Renal physiology · 2022Article
- Extracellular Vesicles in Redox Signaling and Metabolic Regulation in Chronic Kidney Disease.Antioxidants (Basel, Switzerland) · 2022Review
- Angiotensinogen and Risk of Stroke Events in Patients with Type 2 Diabetes Mellitus.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Article
- Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease.Frontiers in pharmacology · 2021Review
- Quantification of model and data uncertainty in a network analysis of cardiac myocyte mechanosignalling.Philosophical transactions. Series A, Mathematical, physical, and engineering sciences · 2020Article
- Urinary angiotensinogen increases in the absence of overt renal injury in high fat diet-induced type 2 diabetic mice.Journal of diabetes and its complications · 2020Article
- Blockade of sodium-glucose cotransporter 2 suppresses high glucose-induced angiotensinogen augmentation in renal proximal tubular cells.American journal of physiology. Renal physiology · 2020Article
- Hydrogen Sulfide: Recent Progression and Perspectives for the Treatment of Diabetic Nephropathy.Molecules (Basel, Switzerland) · 2019Review
- Advanced Glycation End Products Stimulate Angiotensinogen Production in Renal Proximal Tubular Cells.The American journal of the medical sciences · 2019Article
- Independent regulation of renin-angiotensin-aldosterone system in the kidney.Clinical and experimental nephrology · 2018Review
- Role of the intrarenal renin-angiotensin system in the progression of renal disease.Pediatric nephrology (Berlin, Germany) · 2017Review
- Increased angiotensinogen expression, urinary angiotensinogen excretion, and tissue injury in nonclipped kidneys of two-kidney, one-clip hypertensive rats.American journal of physiology. Renal physiology · 2016Article
- Urinary Cyclophilin A as a New Marker for Diabetic Nephropathy: A Cross-Sectional Analysis of Diabetes Mellitus.Medicine · 2015Observational
- Changes in urinary angiotensinogen posttreatment in pediatric IgA nephropathy patients.Pediatric nephrology (Berlin, Germany) · 2015Article
- Renoprotective effects of direct renin inhibition in glomerulonephritis.The American journal of the medical sciences · 2014Article
- ROCK/NF-κB axis-dependent augmentation of angiotensinogen by angiotensin II in primary-cultured preglomerular vascular smooth muscle cells.American journal of physiology. Renal physiology · 2014Article
- Article
- Urinary excretion of RAS, BMP, and WNT pathway components in diabetic kidney disease.Physiological reports · 2014Article
- Detailed localization of augmented angiotensinogen mRNA and protein in proximal tubule segments of diabetic kidneys in rats and humans.International journal of biological sciences · 2014Article
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Abstract
Whereas intra-renal angiotensinogen is predominantly localized in proximal tubular cells under basal conditions, it has been previously reported that angiotensinogen expression is induced in glomeruli under pathological conditions. However, there is no detailed information regarding the mechanism of the induced glomerular angiotensinogen. We used genetic pairs of Zucker diabetic fatty (ZDF) obese and lean rats to determine glomerular angiotensinogen expression. The levels of glomerular angiotensinogen immunoreactivity in ZDF obese rats were higher than those in ZDF lean rats. Double staining by IHC or IF with angiotensinogen and Thy1.1 antibodies showed that the majority of angiotensinogen in glomeruli was seen in mesangial cells. The levels of glomerular immunoreactivity for 4-HNE and urinary excretion of 8-isoprostane-markers of ROS-in ZDF obese rats were higher than those in ZDF lean rats. To confirm this system, primary rat mesangial cells were treated with hydrogen peroxide (H₂O₂) to clarify the signal transduction pathway for glomerular angiotensinogen expression. H₂O₂ induced an increase in angiotensinogen expression in a dose- and time-dependent manner, and the H₂O₂-induced upregulation of angiotensinogen was suppressed by catalase. Furthermore, the H₂O₂-induced upregulation of angiotensinogen was inhibited by a mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor and a c-Jun N-terminal kinase (JNK) inhibitor, but not inhibited by a p38 MAPK inhibitor. These data suggest that the majority of angiotensinogen was induced in mesangial cells in glomeruli under pathological conditions such as diabetic nephropathy, and angiotensinogen expression in mesangial cells was mediated by H₂O₂ and the subsequent activation of extracellular-regulated kinase (ERK)/JNK pathways.
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