Tissue-specific expression of renin-angiotensin system components in IgA nephropathy.
BACKGROUND
The renin-angiotensin II system (RAS) has been implicated in the development of glomerulonephritis. The aims of this study were to determine (1) the expression of RAS components, angiotensin (Ang II)-forming enzymes [angiotensin-I-converting enzyme (ACE) and chymase], and Ang II receptors, and (2) the correlation between RAS expression and severity of tissue injury in IgA nephropathy (IgAN).


METHODS
The expression levels of ACE, chymase, and Ang II type 1 and type 2 receptor (AT1R and AT2R) mRNAs were determined by in situ hybridization in renal specimens from 18 patients with IgAN, 5 patients with non-IgA mesangial proliferative glomerulonephritis (non-IgAN) and 10 patients with nonmesangial proliferative glomerulonephritis (minimal change nephrotic syndrome, n = 5, and membranous nephropathy, n = 5). Normal portions of surgically resected kidney served as control.


RESULTS
In normal kidney, a few mesangial cells and glomerular and tubular epithelial cells weakly expressed ACE, chymase and AT1R mRNAs. In IgAN and non-IgAN samples, ACE, chymase, AT1R and AT2R mRNAs were expressed in resident glomerular cells, including mesangial cells, glomerular epithelial cells and cells of Bowman's capsule. The glomerular expressions in IgAN were stronger than in minimal change nephrotic syndrome and membranous nephropathy. In IgAN, the expressions in glomeruli correlated with the degree of mesangial hypercellularity, whereas the expression levels were weaker at the area of mesangial expansion. IgAN with severe tubulointerstitial injury showed expression of ACE, chymase, AT1R and AT2R mRNAs in atrophic tubules and infiltrating cells and such expression correlated with the degree of tubulointerstitial damage.


CONCLUSIONS
Our results suggest that renal cells can produce RAS components and that locally synthesized Ang II may be involved in tissue injury in IgAN through Ang II receptors in the kidney.
Miyake-Ogawa
Chie
C
Division of Nephrology, Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Miyazaki
Masanobu
M
Abe
Katsushige
K
Harada
Takashi
T
Ozono
Yoshiyuki
Y
Sakai
Hideto
H
Koji
Takehiko
T
Kohno
Shigeru
S
D000328:Adult; D000804:Angiotensin II / Q000096:biosynthesis; D016022:Case-Control Studies; D053818:Chymases; D005920:Glomerular Mesangium / Q000378:metabolism; D005921:Glomerulonephritis / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D007678:Kidney Glomerulus / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011945:Receptors, Angiotensin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology*; D012697:Serine Endopeptidases / Q000378:metabolism
D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; D012697:Serine Endopeptidases; D053818:Chymases