Insulin Receptor Substrate p53 Ameliorates High-Glucose-Induced Activation of NF-κB and Impaired Mobility of HUVECs.
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 (HUV...
| Publicado en: | BioMed Research International pp. 1 - 12 |
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| Autores principales: | , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
1/12/2021
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=148071222&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 148071222 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 1/12/2021 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 148071222 148071222 148071222 10.1155/2021/3210586 148071222 ppf: 1 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Insulin Receptor Substrate p53 Ameliorates High-Glucose-Induced Activation of NF-κB and Impaired Mobility of HUVECs. aug: au: Liu, Fen Chen, Yubin Zhao, Shi Li, Mei Luo, Fanyan Tang, Can-e affil: The Institute of Medical Science Research, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China sug: subj: Insulin NF-kappa B Blood Glucose Umbilical Veins Endothelial Cells Animal Studies Rats Diabetes Mellitus Hyperglycemia Gene Expression RNA ab: 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. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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