title: Glomerular angiotensin-converting enzyme 2 in pediatric IgA nephropathy.
abstract: BACKGROUND
  Angiotensin-converting enzyme (ACE) 2 is a homolog of ACE and is thought to be a potent counter-regulator against ACE activity. However, the role of ACE2 has not been investigated in pediatric patients with IgA nephropathy (IgAN). This study was performed to examine the relationship between ACE2 expression and the development of pediatric IgAN.
  
  
  METHODS
  We performed immunohistochemical analysis of ACE2 and ACE in 39 patients with pediatric IgAN and 14 patients with minor glomerular abnormalities, and elucidated the effects of various cytokines on ACE2 expression in cultured human mesangial cells.
  
  
  RESULTS
  ACE2 expression levels in glomeruli and tubules were positively correlated with the mesangial hypercellularity score, while ACE expression levels in glomeruli and tubules are not. Multiple regression analysis showed that the mesangial hypercellularity score correlated with the ACE2 expression level in glomeruli and the urinary protein-creatinine ratio. In IgAN patients not treated with a renin-angiotensin system blocker, ACE2 expression levels in glomeruli were significantly increased compared to patients with minor glomerular abnormalities. IgAN patients treated with a renin-angiotensin system blocker did not show this increase in ACE2 expression. Furthermore, cultured human MC showed increased ACE2 mRNA and protein after treatment with IL-1β, a pro-inflammatory cytokine in IgAN. In fact, glomerular expressions of IL-1β were remarkably increased in patients with IgAN.
  
  
  CONCLUSIONS
  These data indicate that ACE2 expression in glomeruli is associated with mesangial hypercellularity in early lesions of pediatric IgAN.
authors.affiliation: Department of Pediatrics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Urushihara
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Seki
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tayama
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagai
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Ariunbold
authors.initials: A
authors.lastname: Jamba
authors.forename: Shuji
authors.initials: S
authors.lastname: Kondo
authors.forename: Shoji
authors.initials: S
authors.lastname: Kagami
mesh_terms: D000293:Adolescent; D000085962:Angiotensin-Converting Enzyme 2; D001706:Biopsy; D002478:Cells, Cultured; D002648:Child; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D005922:Glomerulonephritis, IGA / Q000175:diagnosis* / Q000201:enzymology*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007678:Kidney Glomerulus / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D050527:Mesangial Cells / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012044:Regression Analysis; D012084:Renin-Angiotensin System
chemical_list: D012333:RNA, Messenger; D003404:Creatinine; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2