Diabetes Care
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Diabetes Care 29:848-852, 2006
DOI: 10.2337/diacare.29.04.06.dc05-1873
© 2006 by the American Diabetes Association
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Pathophysiology/Complications
Original Article

Tissue Gene Expression of Renin-Angiotensin System in Human Type 2 Diabetic Nephropathy

Tadashi Konoshita, MD, PHD1, Shigeyuki Wakahara, MD1, Shinichi Mizuno1, Makoto Motomura1, Chikako Aoyama1, Yasukazu Makino, MD1, Yasuyuki Kawai, MD, PHD1, Norihiro Kato, MD, PHD2, Ichiro Koni, MD, PHD3, Isamu Miyamori, MD, PHD1 and Hiroshi Mabuchi, MD, PHD3

1 Third Department of Internal Medicine, Fukui University School of Medicine, Fukui, Japan
2 Department of Gene Diagnostics and Therapeutics, Research Institute, International Medical Center of Japan, Tokyo, Japan
3 Second Department of Internal Medicine, Kanazawa University Graduate School of Medicine, Kanazawa, Japan

Address correspondence and reprint requests to Tadashi Konoshita, Third Department of Internal Medicine, Fukui University School of Medicine, 23-3, Shimoaizuki, Matsuoka, Fukui, 910-1193, Japan. E-mail: konosita{at}fmsrsa.fukui-med.ac.jp

OBJECTIVE—Recent studies have proved that blockade of the renin-angiotensin system (RAS) retards the progression of diabetic nephropathy, whereas hyporeninemia is known as a typical state in diabetic subjects. The purpose of this study is to determine whether expression levels of RAS differ between nondiabetic and diabetic renal tissues with accurate quantitative method.

RESEARCH DESIGN AND METHODS—Subjects were 66 nondiabetic and 8 diabetic patients with biopsy-proven renal diseases. The eight diabetic subjects suffered from type 2 diabetes with overt proteinuria. Renal histology revealed typical diffuse or nodular lesions with linear IgG deposit on immunofluorescent staining and thickened basement membrane on electronic microscopy. Total RNA from a small part of the renal cortical biopsy specimens was reverse-transcribed, and the resultant cDNA was amplified for new major components of RAS (i.e., renin, renin receptor, angiotensinogen, ACE, ACE2, angiotensin II type 1 receptor, and angiotensin II type 2 receptor) and measured.

RESULTS—Among these components, a significant upregulation was observed in the ACE gene in diabetic renal tissue.

CONCLUSIONS—The results suggest that renal tissue RAS might be activated in the respect that ACE gene expression is upregulated in spite of a tendency to low renin expression in type 2 diabetic nephropathy.

Abbreviations: AGT, angiotensinogen • ARB, angiotensin II receptor blocker • AT1, angiotensin II type 1 receptor • AT2, angiotensin II type 2 receptor • GAPDH, glyceraldehyde-3-phosphate dehydrogenase • RAS, renin-angiotensin system • RER, renin receptor • sBP, systolic blood pressure


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Copyright © 2006 by the American Diabetes Association.