INTRODUCTION: 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. DISCUSSION: 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.
INTRODUCTION: 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 IIAT(1) receptor (AT(1)R) antagonist candesartan, but not by the AT(2) receptor (AT(2)R) antagonist PD123319. DISCUSSION: 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: Saraswati Kache; Mohammod Jobayer Chisti; Felicity Gumbo; Ezekiel Mupere; Xia Zhi; Karthi Nallasamy; Satoshi Nakagawa; Jan Hau Lee; Matteo Di Nardo; Pedro de la Oliva; Chhavi Katyal; Kanwaljeet J S Anand; Daniela Carla de Souza; Vanessa Soares Lanziotti; Joseph Carcillo Journal: Pediatr Res Date: 2020-07-07 Impact factor: 3.756
Authors: Michelle Elena Schober; Courtney Leigh Robertson; Mark Stephen Wainwright; Juan David Roa; Ericka Linn Fink Journal: Neurocrit Care Date: 2021-06-28 Impact factor: 3.210
Authors: A Aleksova; F Ferro; G Gagno; C Cappelletto; D Santon; M Rossi; G Ippolito; A Zumla; A P Beltrami; G Sinagra Journal: J Intern Med Date: 2020-06-08 Impact factor: 13.068
Authors: Hajira Dambha-Miller; Ali Albasri; Sam Hodgson; Christopher R Wilcox; Shareen Khan; Nazrul Islam; Paul Little; Simon J Griffin Journal: BMJ Open Date: 2020-09-14 Impact factor: 2.692