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...

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Main Authors:	Fen Liu, Yubin Chen, Shi Zhao, Mei Li, Fanyan Luo, Can-e Tang
Format:	Article
Language:	English
Published:	Hindawi Limited 2021-01-01
Series:	BioMed Research International
Online Access:	http://dx.doi.org/10.1155/2021/3210586

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spelling	doaj-d634fcd60f3e4544ba1e41b6f263c4552021-02-15T12:52:43ZengHindawi LimitedBioMed Research International2314-61332314-61412021-01-01202110.1155/2021/32105863210586Insulin Receptor Substrate p53 Ameliorates High-Glucose-Induced Activation of NF-κB and Impaired Mobility of HUVECsFen Liu0Yubin Chen1Shi Zhao2Mei Li3Fanyan Luo4Can-e Tang5The Institute of Medical Science Research, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, ChinaDepartment of Cardiac Surgery, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, ChinaThe Institute of Medical Science Research, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, ChinaThe Institute of Medical Science Research, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, ChinaDepartment of Cardiac Surgery, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, ChinaThe Institute of Medical Science Research, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, ChinaDiabetes-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.http://dx.doi.org/10.1155/2021/3210586
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Fen Liu Yubin Chen Shi Zhao Mei Li Fanyan Luo Can-e Tang
spellingShingle	Fen Liu Yubin Chen Shi Zhao Mei Li Fanyan Luo Can-e Tang Insulin Receptor Substrate p53 Ameliorates High-Glucose-Induced Activation of NF-κB and Impaired Mobility of HUVECs BioMed Research International
author_facet	Fen Liu Yubin Chen Shi Zhao Mei Li Fanyan Luo Can-e Tang
author_sort	Fen Liu
title	Insulin Receptor Substrate p53 Ameliorates High-Glucose-Induced Activation of NF-κB and Impaired Mobility of HUVECs
title_short	Insulin Receptor Substrate p53 Ameliorates High-Glucose-Induced Activation of NF-κB and Impaired Mobility of HUVECs
title_full	Insulin Receptor Substrate p53 Ameliorates High-Glucose-Induced Activation of NF-κB and Impaired Mobility of HUVECs
title_fullStr	Insulin Receptor Substrate p53 Ameliorates High-Glucose-Induced Activation of NF-κB and Impaired Mobility of HUVECs
title_full_unstemmed	Insulin Receptor Substrate p53 Ameliorates High-Glucose-Induced Activation of NF-κB and Impaired Mobility of HUVECs
title_sort	insulin receptor substrate p53 ameliorates high-glucose-induced activation of nf-κb and impaired mobility of huvecs
publisher	Hindawi Limited
series	BioMed Research International
issn	2314-6133 2314-6141
publishDate	2021-01-01
description	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.
url	http://dx.doi.org/10.1155/2021/3210586
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Insulin Receptor Substrate p53 Ameliorates High-Glucose-Induced Activation of NF-κB and Impaired Mobility of HUVECs

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