Our previous study revealed that Homeobox containing 1 (HMBOX1), essential for the survival of vascular endothelial cells (VECs), was involved in the progression of atherosclerosis. Knockdown of HMBOX1 promoted apoptosis and inhibited autophagy through regulating intracellular free zinc level in cultured VECs. In current study, in order to investigate the roles of HMBOX1 in vivo and in endothelium, we generated a knockout (KO) mouse for HMBOX1 by using transcription activator-like effector nucleases (TALENs) technology. Herein, we reported that the protein level of HMBOX1 was gradually increased during mouse development. The HMBOX1 KO mouse was viable and fertile. There existed no differences in apoptosis and autophagy of aortic endothelial cells between wild type and KO mouse. Whereas, loss of HMBOX1 promoted apoptosis and inhibited autophagy of aortic endothelial cells under lipopolysaccharide (LPS) stimulation in mouse. We also demonstrated that HMBOX1 deletion had no influence on the secretion of inflammatory cytokines TNF-α and IL-6. Moreover, overexpression or knockdown of HMBOX1 failed to regulate multiple pro-apoptotic genes expression in vitro. In conclusion, HMBOX1 participated in the functional maintenance of mouse aortic endothelial cells, the aortic endothelial cells of HMBOX1 KO mouse showed increased apoptosis and decreased autophagy with LPS treatment.

中文翻译：

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HMBOX1的丢失促进LPS诱导的小鼠凋亡，并抑制LPS诱导的小鼠血管内皮细胞自噬。

我们以前的研究表明，含有1（HMBOX1）的Homeobox对血管内皮细胞（VEC）的生存至关重要，它参与了动脉粥样硬化的发展。敲低HMBOX1可以通过调节培养的VECs中的细胞内游离锌水平来促进细胞凋亡并抑制自噬。在当前的研究中，为了研究HMBOX1在体内和内皮中的作用，我们通过使用转录激活因子样效应子核酸酶（TALENs）技术为HMBOX1产生了敲除（KO）小鼠。在本文中，我们报道了HMBOX1的蛋白质水平在小鼠发育过程中逐渐增加。HMBOX1 KO小鼠具有活力和繁殖力。野生型和KO小鼠在主动脉内皮细胞凋亡和自噬方面没有差异。鉴于，HMBOX1的缺失促进了小鼠脂多糖（LPS）刺激下主动脉内皮细胞的凋亡并抑制了其自噬。我们还证明了HMBOX1缺失对炎性细胞因子TNF-α和IL-6的分泌没有影响。此外，HMBOX1的过表达或敲低未能在体外调节多个促凋亡基因的表达。综上所述，HMBOX1参与了小鼠主动脉内皮细胞的功能维持，通过LPS处理，HMBOX1 KO小鼠的主动脉内皮细胞凋亡增加，自噬减少。HMBOX1的过表达或敲低未能在体外调节多个促凋亡基因的表达。综上所述，HMBOX1参与了小鼠主动脉内皮细胞的功能维持，通过LPS处理，HMBOX1 KO小鼠的主动脉内皮细胞凋亡增加，自噬减少。HMBOX1的过表达或敲低未能在体外调节多个促凋亡基因的表达。综上所述，HMBOX1参与了小鼠主动脉内皮细胞的功能维持，通过LPS处理，HMBOX1 KO小鼠的主动脉内皮细胞凋亡增加，自噬减少。