ArticleJournal of the American Society of Nephrology : JASN2008
Products of 12/15-lipoxygenase upregulate the angiotensin II receptor.
Article in Journal of the American Society of Nephrology : JASN, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- Pravastatin Therapy and Biomarker Changes in Children and Young Adults with Autosomal Dominant Polycystic Kidney Disease.Clinical journal of the American Society of Nephrology : CJASN · 2015Trial
- Bioactive lipid mediators in polycystic kidney disease.Journal of lipid research · 2014Trial
- Central Interaction of 2-Methoxyestradiol and Lipoxygenase in AngII-Hypertension.Hypertension (Dallas, Tex. : 1979) · 2025Article
- Effects of Inflammatory Factor Expression Regulated by 12/15 Lipoxygenase on Obesity-Related Nephropathy.Nutrients · 2022Article
- 15-Lipoxygenase worsens renal fibrosis, inflammation, and metabolism in a murine model of ureteral obstruction.American journal of physiology. Renal physiology · 2022Article
- Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications.Pharmacology & therapeutics · 2019Review
- Clinical Trials in Pediatric Autosomal Dominant Polycystic Kidney Disease.Frontiers in pediatrics · 2017Review
- 12-Lipoxygenase Inhibition on Microalbuminuria in Type-1 and Type-2 Diabetes Is Associated with Changes of Glomerular Angiotensin II Type 1 Receptor Related to Insulin Resistance.International journal of molecular sciences · 2016Article
- Epigenetic Histone Modifications Involved in Profibrotic Gene Regulation by 12/15-Lipoxygenase and Its Oxidized Lipid Products in Diabetic Nephropathy.Antioxidants & redox signaling · 2016Article
- Cytochrome P450 and Lipoxygenase Metabolites on Renal Function.Comprehensive Physiology · 2015Review
- Eicosanoid post-mortem induction in kidney tissue is prevented by microwave irradiation.Prostaglandins, leukotrienes, and essential fatty acids · 2013Article
- Effects of lovastatin treatment on the metabolic distributions in the Han:SPRD rat model of polycystic kidney disease.BMC nephrology · 2013Article
- 12S-hydroxyeicosatetraenoic acid levels link to coronary artery disease in Type 2 diabetic patients.Journal of endocrinological investigation · 2013Article
- Regulation of renal 12(S)-hydroxyeicosatetraenoic acid in diabetes by angiotensin AT1 and AT2 receptors.American journal of physiology. Regulatory, integrative and comparative physiology · 2008Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Angiotensin II and its type 1 receptor (AT1R) play important roles in the pathogenesis of renal disease and diabetic nephropathy. The 12/15-lipoxygenase pathway of arachidonate metabolism and its lipid products have also been implicated in diabetic nephropathy. However, it is unclear whether 12/15-lipoxygenase regulates expression of AT1R. In cultured rat mesangial cells, we found that the 12/15-lipoxygenase product 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) increased AT1R mRNA and protein expression, primarily by stabilizing AT1R mRNA. Pretreatment with 12(S)-HETE also amplified the signaling effects of angiotensin II, likely due to the increased AT1R expression. Levels of AT1R protein expression decreased when 12/15-lipoxygenase was knocked down with specific short hairpin RNA (shRNA) compared with control cells. Similarly, levels of the AT1 receptor, but not the AT2 receptor, were significantly lower in mesangial cells and glomeruli derived from 12/15-lipoxygenase knockout mice compared with control mice. Reciprocally, stable overexpression of 12/15-lipoxygenase increased AT1R expression in cultured mesangial cells. In vivo, modified siRNA targeting 12/15-lipoxygenase reduced glomerular AT1R expression in a diabetic mouse model. Interestingly, angiotensin II induced greater levels of 12/15-lipoxygenase, TGF-beta1, and fibronectin (FN) in AT1R-overexpressing mesangial cells compared with control cells. Therefore, oxidized lipids generated by the 12/15-lipoxygenase-mediated metabolism of arachidonic acid can enhance AT1R expression in mesangial cells and augment the profibrotic effects of angiotensin II.
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