title: Ablation of SGK1 impairs endothelial cell migration and tube formation leading to decreased neo-angiogenesis following myocardial infarction.
abstract: Serum and glucocorticoid inducible kinase 1 (SGK1) plays a pivotal role in early angiogenesis during embryonic development. In this study, we sought to define the SGK1 downstream signalling pathways in the adult heart and to elucidate their role in cardiac neo-angiogenesis and wound healing after myocardial ischemia. To this end, we employed a viable SGK1 knockout mouse model generated in a 129/SvJ background. Ablation of SGK1 in these mice caused a significant decrease in phosphorylation of SGK1 target protein NDRG1, which correlated with alterations in NF-κB signalling and expression of its downstream target protein, VEGF-A. Disruption of these signalling pathways was accompanied by smaller heart and body size. Moreover, the lack of SGK1 led to defective endothelial cell (ECs) migration and tube formation in vitro, and increased scarring with decreased angiogenesis in vivo after myocardial infarct. This study underscores the importance of SGK1 signalling in cardiac neo-angiogenesis and wound healing after an ischemic insult in vivo.
authors.affiliation: Heart Science Centre, National Heart and Lung Institute, Imperial College London, Harefield, United Kingdom.
authors.forename: Elham
authors.initials: E
authors.lastname: Zarrinpashneh
authors.forename: Tommaso
authors.initials: T
authors.lastname: Poggioli
authors.forename: Padmini
authors.initials: P
authors.lastname: Sarathchandra
authors.forename: Jonas
authors.initials: J
authors.lastname: Lexow
authors.forename: Laurent
authors.initials: L
authors.lastname: Monassier
authors.forename: Cesare
authors.initials: C
authors.lastname: Terracciano
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Federico
authors.initials: F
authors.lastname: Damilano
authors.forename: Jessica Q
authors.initials: JQ
authors.lastname: Zhou
authors.forename: Anthony
authors.initials: A
authors.lastname: Rosenzweig
authors.forename: Nadia
authors.initials: N
authors.lastname: Rosenthal
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Santini
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D048429:Cell Size; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism*; D005355:Fibrosis; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D017202:Myocardial Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D015398:Signal Transduction; D000099184:Serum-Glucocorticoid Regulated Kinases; D000099259:N-myc Downstream-Regulated Gene 1 Protein
chemical_list: D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D017346:Protein Serine-Threonine Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases; D000099259:N-myc Downstream-Regulated Gene 1 Protein