title: Ontogeny of angiotensin-converting enzyme 2.
abstract: BACKGROUND
  This study examined the temporal expression of angiotensin (Ang)-converting enzyme 2 (ACE2) during renal, heart, lung, and brain organogenesis in the mouse.
  
  
  RESULTS
  We demonstrate that kidney ACE2 mRNA levels are low on embryonic day (E) 12.5, increase fourfold during development, and decline in adulthood. In extrarenal tissues, ACE2 mRNA levels are also low during early gestation, increase in perinatal period, and peak in adulthood. The lung shows the highest age-related increase in ACE2 mRNA levels followed by the brain, kidney, and heart. ACE2 protein levels and enzymatic activity are high in all organs studied during gestation and decline postnatally. Ang II decreases ACE2 mRNA levels and enzymatic activity in kidneys grown ex vivo. These effects of Ang II are blocked by the specific Ang II AT(1) receptor (AT(1)R) antagonist candesartan, but not by the AT(2) receptor (AT(2)R) antagonist PD123319.
  
  
  CONCLUSIONS
  We conclude that ACE2 gene and protein expression and enzymatic activity are developmentally regulated in a tissue-specific manner. Ang II, acting through AT(1)R, exerts a negative feedback on ACE2 during kidney development. We postulate that relatively high ACE2 protein levels and enzymatic activity observed during gestation may play a role in kidney, lung, brain, and heart organogenesis.
authors.affiliation: Department of Pediatrics, Tulane University School of Medicine, New Orleans, Louisiana, USA.
authors.forename: Renfang
authors.initials: R
authors.lastname: Song
authors.forename: Graeme
authors.initials: G
authors.lastname: Preston
authors.forename: Ihor V
authors.initials: IV
authors.lastname: Yosypiv
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001921:Brain / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000033:anatomy & histology / Q000502:physiology; D007668:Kidney / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D008168:Lung / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000166:cytology / Q000201:enzymology; D038081:Organogenesis / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2