The Institute of Medical Science Research, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China.
Department of Cardiac Surgery, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China.
Biomed Res Int. 2021 Jan 6;2021:3210586. doi: 10.1155/2021/3210586. eCollection 2021.
Diabetes-related macrovascular and microvascular complications lead to poor prognosis. Insulin receptor substrate p53 (IRSp53) is known to act as a substrate for the insulin receptor tyrosine kinase, but its role in endothelial dysfunction remains unclear. Human umbilical vein endothelial cells (HUVECs) treated with D-glucose at different concentrations and a streptozocin-induced rat diabetes mellitus (DM) model were used to investigate the effects of hyperglycemia on the expression levels of IRSp53 and galectin-3 (gal-3) and the inflammatory state and mobility of HUVECs. Thereafter, IRSp53-overexpressing HUVECs and IRSp53-knockdown HUVECs were established using IRSp53-overexpressing lentivirus or IRSp53-siRNA to explore the role of IRSp53 in the HUVEC inflammatory state and HUVEC mobility. D-glucose at high concentration (HG) and hyperglycemia were found to induce downregulation of IRSp53 and upregulation of gal-3 and . Treatment with HG resulted in activation of NF-B in HUVECs and impaired HUVEC mobility. Insulin restored HG-induced changes in the expression levels of IRSp53 and gal-3 in HUVECs and protected the cells from NF-B activation and impaired mobility. Overexpression of IRSp53 inhibited the activation of NF-B in HUVECs and strengthened HUVEC migration. Knockdown of IRSp53 facilitated the activation of NF-B in HUVECs and decreased HUVEC migration. However, neither overexpression nor knockdown of IRSp53 altered the effects of insulin on HG-induced detrimental changes in HUVECs. HG and hyperglycemia resulted in downregulation of IRSp53 and . IRSp53 is concluded to inhibit the activation of NF-B in HUVECs and to strengthen HUVEC migration.
糖尿病相关的大血管和微血管并发症导致预后不良。胰岛素受体底物 p53（IRSp53）已知作为胰岛素受体酪氨酸激酶的底物起作用，但其在血管内皮功能障碍中的作用尚不清楚。用人脐静脉内皮细胞（HUVEC）在不同浓度的 D-葡萄糖和链脲佐菌素诱导的大鼠糖尿病（DM）模型中，研究高血糖对 IRSp53 和半乳糖凝集素-3（gal-3）表达水平以及 HUVEC 炎症状态和迁移的影响。此后，使用 IRSp53 过表达慢病毒或 IRSp53-siRNA 建立 IRSp53 过表达 HUVEC 和 IRSp53 敲低 HUVEC，以探讨 IRSp53 在 HUVEC 炎症状态和 HUVEC 迁移中的作用。高浓度 D-葡萄糖（HG）和高血糖被发现诱导 IRSp53 下调和 gal-3 的上调。HG 处理导致 HUVEC 中 NF-B 的激活和 HUVEC 迁移受损。胰岛素恢复了 HG 诱导的 HUVEC 中 IRSp53 和 gal-3 表达水平的变化，并保护细胞免受 NF-B 激活和迁移受损的影响。IRSp53 的过表达抑制了 HUVEC 中 NF-B 的激活并增强了 HUVEC 迁移。IRSp53 的敲低促进了 HUVEC 中 NF-B 的激活并降低了 HUVEC 迁移。然而，IRSp53 的过表达或敲低均不改变胰岛素对 HG 诱导的 HUVEC 有害变化的影响。HG 和高血糖导致 IRSp53 的下调和。IRSp53 被认为抑制了 HUVEC 中 NF-B 的激活并增强了 HUVEC 迁移。
