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

被引:60
作者
Kamiyama, Masumi [1 ,2 ]
Urushihara, Maki [1 ,2 ]
Morikawa, Takashi [3 ]
Konishi, Yoshio [3 ]
Imanishi, Masahito [3 ]
Nishiyama, Akira [4 ]
Kobori, Hiroyuki [1 ,2 ,4 ,5 ]
机构
[1] Tulane Univ, Hlth Sci Ctr, Dept Physiol, New Orleans, LA 70112 USA
[2] Tulane Univ, Hypertens & Renal Ctr Excellence, Hlth Sci Ctr, New Orleans, LA 70112 USA
[3] Osaka City Gen Hosp, Dept Hypertens & Nephrol, Miyakojima Ku, Osaka 5340021, Japan
[4] Kagawa Univ, Dept Pharmacol, Sch Med, Miki, Kagawa 7610793, Japan
[5] Tulane Univ, Dept Med, Hlth Sci Ctr, New Orleans, LA 70112 USA
关键词
angiotensinogen; clinical study; diabetic nephropathy; oxidative stress; renin-angiotensin system; PROXIMAL TUBULE SEGMENTS; URINARY ANGIOTENSINOGEN; GENE-EXPRESSION; MESSENGER-RNA; RENAL INJURY; MESANGIAL CELLS; II BLOCKADE; RENIN; GLUCOSE; BIOMARKER;
D O I
10.3390/ijms141123045
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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.
引用
收藏
页码:23045 / 23062
页数:18
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