title: Oxidative stress/angiotensinogen/renin-angiotensin system axis in patients with diabetic nephropathy.
abstract: Although recent studies have proven that renin-angiotensin system (RAS) blockades retard the progression of diabetic nephropathy, the detailed mechanisms of their reno-protective effects on the development of diabetic nephropathy remain uncertain. In rodent models, it has been reported that reactive oxygen species (ROS) are important for intrarenal angiotensinogen (AGT) augmentation in the progression of diabetic nephropathy. However, no direct evidence is available to demonstrate that AGT expression is enhanced in the kidneys of patients with diabetes. To examine whether the expression levels of ROS- and RAS-related factors in kidneys are increased with the progression of diabetic nephropathy, biopsied samples from 8 controls and 27 patients with type 2 diabetes were used. After the biopsy, these patients were diagnosed with minor glomerular abnormality or diabetes mellitus by clinical and pathological findings. The intensities of AGT, angiotensin II (Ang II), 4-hydroxy-2-nonenal (4-HNE), and heme oxygenase-1 (HO-1) were examined by fluorescence in situ hybridization and/or immunohistochemistry. Expression levels were greater in patients with diabetes than in control subjects. Moreover, the augmented intrarenal AGT mRNA expression paralleled renal dysfunction in patients with diabetes. These data suggest the importance of the activated oxidative stress/AGT/RAS axis in the pathogenesis of diabetic nephropathy.
authors.affiliation: Department of Physiology, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA. hkobori@tulane.edu.
authors.forename: Masumi
authors.initials: M
authors.lastname: Kamiyama
authors.forename: Maki
authors.initials: M
authors.lastname: Urushihara
authors.forename: Takashi
authors.initials: T
authors.lastname: Morikawa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Konishi
authors.forename: Masahito
authors.initials: M
authors.lastname: Imanishi
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobori
mesh_terms: D000328:Adult; D000447:Aldehydes / Q000378:metabolism; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics / Q000473:pathology; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics*
chemical_list: D000447:Aldehydes; D017382:Reactive Oxygen Species; D000808:Angiotensinogen; D051547:Heme Oxygenase-1; C027576:4-hydroxy-2-nonenal