Increased ACE and decreased ACE2 expression in kidneys from patients with IgA nephropathy.
BACKGROUND
Angiotensin-converting enzyme (ACE)2 forms angiotensin-1-7 which may protect kidney in a counterregulatory manner to angiotensin II. Recent studies revealed increased ACE and decreased ACE2 expression in kidneys of patients with diabetic nephropathy. However, these changes may not be specific for diabetic nephropathy. We studied ACE and ACE2 expression in patients with IgA nephropathy.


METHODS
Renal ACE and ACE2 expression was assessed by immunohistochemistry and in situ hybridization in 30 patients with IgA nephropathy and 21 healthy controls. Correlation between ACE and ACE2 expression and levels of various biochemical parameters was also assessed. Gene expression was also assessed in minimal change nephrotic syndrome (MCNS) and membranous nephropathy (MN) as disease controls.


RESULTS
Reduced ACE2 expression (p < 0.01) and increased ACE expression in glomeruli (p < 0.001), and reduced ACE2 expression in tubulointerstitium (p < 0.001) were observed in patients with IgA nephropathy compared to healthy controls, although the changes in ACE2 mRNA were not statistically significant. Reduced renal ACE2 expression was also found in MN but not in MCNS. Correlation between renal ACE and ACE2 expression and proteinuria was not observed in IgA nephropathy.


CONCLUSIONS
IgA nephropathy is associated with increased ACE and decreased ACE2 expression in kidneys, as in diabetic nephropathy.
Mizuiri
Sonoo
S
Department of Nephrology, Toho University School of Medicine, Ohta-ku, Tokyo, Japan. sm210@med.toho-u.ac.jp
Hemmi
Hiromichi
H
Arita
Michitsune
M
Aoki
Toshiyuki
T
Ohashi
Yasushi
Y
Miyagi
Moriatsu
M
Sakai
Ken
K
Shibuya
Kazutoshi
K
Hase
Hiroki
H
Aikawa
Atsushi
A
D000328:Adult; D000085962:Angiotensin-Converting Enzyme 2; D005260:Female; D015870:Gene Expression; D005922:Glomerulonephritis, IGA / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015433:Glomerulonephritis, Membranous / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000235:genetics / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D011507:Proteinuria / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D012709:Serum Albumin / Q000378:metabolism; D018709:Statistics, Nonparametric
D012333:RNA, Messenger; D012709:Serum Albumin; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2