Oxidative Stress/Angiotensinogen/Renin-Angiotensin System Axis in Patients with Diabetic Nephropathy

International Journal of Molecular Sciences

Masumi Kamiyama¹  Maki Urushihara¹  Takashi Morikawa²  Yoshio Konishi²  Masahito Imanishi²  Akira Nishiyama³ 

[1] Department of Physiology, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA; E-Mails:;Department of Nephrology and Hypertension, Osaka City General Hospital, 2-13-22 Miyakojima-Hondori, Miyakojima-ku, Osaka 534-0021, Japan; E-Mails:;Department of Pharmacology, Kagawa University Medical School, Miki, 1750-1 Ikenobe, Miki, Kagawa 761-0793, Japan; E-Mail:

关键词: angiotensinogen;    clinical study;    diabetic nephropathy;    oxidative stress;    renin-angiotensin system;   

DOI  :  10.3390/ijms141123045

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2013 by the authors; licensee MDPI, Basel, Switzerland