Nutrition Department, Kunshan Traditional Chinese Medicine Hospital, Kunshan, China.
Nutrition Department, Bayi Hospital Affiliated to Nanjing University of Traditional Chinese Medicine, Nanjing, China.
Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):362-368. doi: 10.1016/j.bbrc.2018.11.041. Epub 2018 Nov 16.
High glucose (HG) induces vascular endothelial cell injury. However, the underlying mechanisms are poorly understood. Circular RNA HIPK3 (circHIPK3) is a highly conserved non-coding RNA. Here we show that circHIPK3 is downregulated in HG-treated human umbilical vein endothelial cells (HUVECs) and in primary aortic endothelial cells (HAECs) from diabetic patients. In both HUVECs and HAECs, lentivirus-mediated circHIPK3 overexpression inhibited HG-induced cell death and apoptosis. Contrarily, circHIPK3 silencing by targeted siRNA exacerbated HG-induced endothelial cell death and apoptosis. Further, circHIPK3 downregulation by HG caused microRNA-124 (miR-124) accumulation in HUVECs and HAECs. On the contrary, miR-124 inhibition by the adeno-associated virus (AAV)-packed miR-124 inhibitor protected endothelial cells from HG. Together, circHIPK3 downregulation mediates HG-induced endothelial cell injury. Targeting circHIPK3-miR-124 pathway could potentially be a novel approach for the treatment of diabetic-associated vascular injury.
高葡萄糖（HG）可诱导血管内皮细胞损伤。然而，其潜在机制尚不清楚。环状 RNA HIPK3（circHIPK3）是一种高度保守的非编码 RNA。在这里，我们发现 HG 处理的人脐静脉内皮细胞（HUVEC）和糖尿病患者的原代主动脉内皮细胞（HAEC）中 circHIPK3 下调。在 HUVEC 和 HAEC 中，慢病毒介导的 circHIPK3 过表达抑制了 HG 诱导的细胞死亡和细胞凋亡。相反，靶向 siRNA 沉默 circHIPK3 加剧了 HG 诱导的内皮细胞死亡和细胞凋亡。此外，HG 引起的 circHIPK3 下调导致 HUVEC 和 HAEC 中 microRNA-124（miR-124）的积累。相反，腺相关病毒（AAV）包装的 miR-124 抑制剂抑制 miR-124 可保护内皮细胞免受 HG 损伤。总之，circHIPK3 的下调介导了 HG 诱导的内皮细胞损伤。靶向 circHIPK3-miR-124 通路可能是治疗糖尿病相关血管损伤的一种新方法。
