Insulin Receptor Substrate p53 Ameliorates High-Glucose-Induced Activation of NF-κB and Impaired Mobility of HUVECs.
Insulin Receptor Substrate p53 Ameliorates High-Glucose-Induced Activation of NF-κB and Impaired Mobility of HUVECs.
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胰岛素受体底物 p53 改善高葡萄糖诱导的 NF-κB 激活和 HUVEC 移动性受损
DOI：
10.1155/2021/3210586
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发表时间：
2021
影响因子：
--
通讯作者：
Tang CE
中科院分区：
文献类型：
--
作者：
Liu F;Chen Y;Zhao S;Li M;Luo F;Tang CE
糖尿病相关的大血管和微血管并发症导致预后不良。已知胰岛素受体底物p53（IRSp 53）作为胰岛素受体酪氨酸激酶的底物，但其在内皮功能障碍中的作用仍不清楚。以不同浓度D-葡萄糖处理的人脐静脉内皮细胞（HUVECs）和链脲佐菌素（STZ）诱导的糖尿病（DM）大鼠模型为研究对象，观察高血糖对HUVECs炎症状态和运动性、IRSp 53和半乳糖凝集素-3（gal-3）表达的影响。此后，使用IRSp 53过表达慢病毒或IRSp 53-siRNA建立IRSp 53过表达的HUVEC和IRSp 53敲低的HUVEC，以探索IRSp 53在HUVEC炎症状态和HUVEC移动性中的作用。高浓度D-葡萄糖（HG）和高血糖可诱导IRSp 53表达下调和gal-3表达上调。HG处理后HUVEC中NF-κB B活化，细胞运动性降低。胰岛素恢复HG诱导的HUVECs中IRSp 53和gal-3表达水平的变化，并保护细胞免受NF-κB活化和受损的运动性。过表达IRSp 53可抑制HUVEC中NF-κB的活化，增强HUVEC的迁移能力。抑制IRSp 53可促进HUVEC中NF-κB的活化，并减少HUVEC的迁移。然而，无论是过表达还是敲低IRSp 53都不能改变胰岛素对HG诱导的HUVECs有害变化的影响。高糖和高血糖可导致IRSp 53在体内外表达下调。IRSp 53可抑制HUVEC中NF-κB的活化，增强HUVEC的迁移能力。
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 in vitro and in vivo. Treatment with HG resulted in activation of NF-κB 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-κB activation and impaired mobility. Overexpression of IRSp53 inhibited the activation of NF-κB in HUVECs and strengthened HUVEC migration. Knockdown of IRSp53 facilitated the activation of NF-κB 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 in vitro and in vivo. IRSp53 is concluded to inhibit the activation of NF-κB in HUVECs and to strengthen HUVEC migration.
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影响因子：
--
作者：
Naudi A;Jove M;Ayala V;Cassanye A;Serrano J;Gonzalo H;Boada J;Prat J;Portero-Otin M;Pamplona R
通讯作者：
Pamplona R
影响因子：
64.5
作者：
Böhni, R;Riesgo-Escovar, J;Hafen, E
通讯作者：
Hafen, E
影响因子：
20.1
作者：
Gimbrone MA Jr;García-Cardeña G
通讯作者：
García-Cardeña G
影响因子：
--
作者：
Carman, Peter J;Dominguez, Roberto
通讯作者：
Dominguez, Roberto
影响因子：
8
作者：
Liu, P-S;Jong, T-H;Leu, T-H
通讯作者：
Leu, T-H