Department of Cardiology, The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, China.
Department of Pharmacy, Jinan Central Hospital Affiliated to Shandong University, Jinan, China.
J Cell Mol Med. 2019 Nov;23(11):7449-7461. doi: 10.1111/jcmm.14613. Epub 2019 Sep 11.
The role of Non-POU-domain-containing octamer-binding protein (NONO) in the formation and development of angiotensin II (Ang II)-induced abdominal aortic aneurysm (AAA) in apolipoprotein E-knockout (ApoE ) mice is still unknown. In Part I, the protein level of NONO was suggestively greater in the AAA tissues compare to that in the normal abdominal aortas. In Part II, 20 ApoE male mice were used to examine the transfection efficiency of lentivirus by detecting GFP fluorescence. In Part III, mice were arbitrarily separated into two groups: one was the control group without Ang II infusion, and another was the Ang II group. Mice treated with Ang II were further randomly divided into three groups to receive the same volume of physiological saline (NT group), sh-negative control lentivirus (sh-NC group) and si-NONO lentivirus (sh-NONO group). NONO silencing suggestively reduced the occurrence of AAA and abdominal aortic diameter. Compare to the NT group, NONO silencing markedly augmented the content of collagen and vascular smooth muscle cells but reduced macrophage infiltration in AAA. In addition, knockdown of NONO also increased the expression of prolyl-4-hydroxylase α1, whereas also decreased the levels of collagen degradation and pro-inflammatory cytokines in AAA. We detected the interface of NONO and NF-κB p65, and found that NONO silencing inhibited both the nuclear translocation and the phosphorylation levels of NF-κB p65. Silencing of NONO prevented Ang II-influenced AAA in ApoE mice through increasing collagen deposition and inhibiting inflammation. The mechanism may be that silencing of NONO decreases the nuclear translocation and phosphorylation of NF-κB.
非 POU 域蛋白结合蛋白（NONO）在载脂蛋白 E 敲除（ApoE）小鼠血管紧张素 II（Ang II）诱导的腹主动脉瘤（AAA）形成和发展中的作用尚不清楚。在第一部分中，与正常腹主动脉相比，NONO 蛋白水平在 AAA 组织中提示更高。在第二部分，使用 20 只 ApoE 雄性小鼠通过检测 GFP 荧光来检测慢病毒的转染效率。在第三部分，将小鼠任意分为两组：一组为不给予 Ang II 输注的对照组，另一组为 Ang II 组。给予 Ang II 的小鼠进一步随机分为三组，分别给予等量的生理盐水（NT 组）、sh-阴性对照慢病毒（sh-NC 组）和 si-NONO 慢病毒（sh-NONO 组）。NONO 沉默提示 AAA 和腹主动脉直径的发生减少。与 NT 组相比，NONO 沉默明显增加 AAA 中胶原蛋白和血管平滑肌细胞的含量，而减少巨噬细胞浸润。此外，NONO 的敲低还增加了脯氨酰-4-羟化酶 α1 的表达，同时降低了 AAA 中胶原蛋白降解和促炎细胞因子的水平。我们检测了 NONO 和 NF-κB p65 的界面，发现 NONO 沉默抑制了 NF-κB p65 的核易位和磷酸化水平。NONO 的沉默通过增加胶原蛋白沉积和抑制炎症来防止 Ang II 影响的 ApoE 小鼠的 AAA。其机制可能是沉默 NONO 减少了 NF-κB 的核易位和磷酸化。
