Tissue gene expression of renin-angiotensin system in human type 2 diabetic nephropathy.
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.


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.
Third Department of Internal Medicine, Fukui University School of Medicine, Matsuoka, Fukui 910-1193, Japan. konosita@fmsrsa.fukui-med.ac.jp
Tadashi
T
Konoshita
Shigeyuki
S
Wakahara
Shinichi
S
Mizuno
Makoto
M
Motomura
Chikako
C
Aoyama
Yasukazu
Y
Makino
Yasuyuki
Y
Kawai
Norihiro
N
Kato
Ichiro
I
Koni
Isamu
I
Miyamori
Hiroshi
H
Mabuchi
D000328:Adult; D000809:Angiotensins / Q000235:genetics* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011507:Proteinuria; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics* / Q000502:physiology; D015854:Up-Regulation; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D000093342:Prorenin Receptor
D000809:Angiotensins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D007703:Peptidyl-Dipeptidase A; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor