Serum and glucocorticoid-inducible kinase 1 (SGK1) is necessary for vascular remodeling during angiogenesis.
The unquestionable importance of the cardiovascular system for pre- and postnatal life has prompted dissection of the molecular mechanisms underlying its development. Serum and glucocorticoid-inducible kinase 1 (SGK1) is a serine/threonine kinase lying downstream of the phosphoinositide 3 (PI3) kinase pathway, whose embryonic function remains unknown. Here, we show that disruption of Sgk1 in the mouse C57BL/6J genetic background leads to embryonic lethality at embryonic day 10.5-11.5 due to severe embryonic and extraembryonic angiogenic defects and to impaired myocardial trabeculation. Absence of SGK1 results in increased apoptosis of endothelial cells, and of vascular smooth muscle cells highlighting a prosurvival role for SGK1 during angiogenesis. Sgk1 null embryos also display reduced expression levels of Notch signaling genes and decreased expression of the arterial markers Efnb2 and Nrp1. These findings uncover a novel and essential function for SGK1 in cardiovascular development contributing to a better understanding of mammalian angiogenesis.
Catela
Catarina
C
EMBL Mouse Biology Unit, Campus A. Buzzati-Traverso, Monterotondo-Scalo (RM), Italy. catarina.catela@mssm.edu
Kratsios
Paschalis
P
Hede
Marianne
M
Lang
Florian
F
Rosenthal
Nadia
N
D000818:Animals; D001808:Blood Vessels / Q000196:embryology* / Q000378:metabolism; D002319:Cardiovascular System / Q000196:embryology / Q000254:growth & development; D002470:Cell Survival; D042783:Endothelial Cells / Q000166:cytology; D017874:Immediate-Early Proteins / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D018919:Neovascularization, Physiologic; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000502:physiology*; D000099184:Serum-Glucocorticoid Regulated Kinases
D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases