Heart Science Centre, National Heart and Lung Institute, Imperial College London, Harefield, United Kingdom.
PLoS One. 2013 Nov 12;8(11):e80268. doi: 10.1371/journal.pone.0080268. eCollection 2013.
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.
血清和糖皮质激素诱导激酶 1（SGK1）在胚胎发育过程中的早期血管生成中发挥关键作用。在这项研究中，我们试图确定成年心脏中的 SGK1 下游信号通路，并阐明它们在心肌缺血后心脏新生血管形成和伤口愈合中的作用。为此，我们使用了在 129/SvJ 背景下生成的可存活的 SGK1 敲除小鼠模型。这些小鼠中 SGK1 的缺失导致 SGK1 靶蛋白 NDRG1 的磷酸化显著减少，这与 NF-κB 信号转导及其下游靶蛋白 VEGF-A 的表达改变相关。这些信号通路的破坏伴随着心脏和身体大小的减小。此外，缺乏 SGK1 导致体外内皮细胞（EC）迁移和管状结构形成受损，以及心肌梗死后体内疤痕形成增加，血管生成减少。这项研究强调了 SGK1 信号在体内缺血性损伤后心脏新生血管形成和伤口愈合中的重要性。
