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. 2025 Mar 30.
doi: 10.1007/s12013-025-01735-0. Online ahead of print.

RNA Binding Protein IGF2BP3 Rehabilitates Glycolysis of Vascular Endothelial Cells to Protect the ox-LDL-induced Cellular Injury via Stabilizing LDHA mRNA

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RNA Binding Protein IGF2BP3 Rehabilitates Glycolysis of Vascular Endothelial Cells to Protect the ox-LDL-induced Cellular Injury via Stabilizing LDHA mRNA

Xing-Chun Mo et al. Cell Biochem Biophys. .

Abstract

Vascular endothelial cells (VECs) dysfunction has been revealed to be a major cause of various cardiovascular diseases. Yet, the precise cellular and molecular mechanisms of VECs injury remain elusive. This study aims to investigate the roles and molecular mechanisms of RNA binding protein IGF2BP3 in vascular endothelial cell injury caused by oxidized low-density lipoprotein (ox-LDL). HUVECs were treated with ox-LDL to induce endothelial cell injury, and the cellular responses to ox-LDL were assessed using cell viability and apoptosis assays. IGF2BP3 was expressed at low levels in vascular tissues from atherosclerosis patients. Treatment with ox-LDL significantly decreased the expression of IGF2BP3 in HUVECs. Overexpression of IGF2BP3 effectively reduced the injury induced by ox-LDL. Glucose metabolism enzymes were significantly downregulated in vascular tissues from atherosclerosis patients and in HUVECs treated with ox-LDL, leading to suppressed glucose metabolism. IGF2BP3 upregulated the glucose metabolism enzyme LDHA to alleviate the injury caused by ox-LDL in HUVECs. Analysis of the LDHA sequence revealed the presence of an IGF2BP3 binding motif in its 3'UTR. Further experiments including RNA pull-down, RNA IP, and RNA stability assays confirmed the specific binding of IGF2BP3 to the 3'UTR region of LDHA, stabilizing its transcripts. Rescue experiments demonstrated that IGF2BP3 mitigated vascular endothelial cell injury by regulating LDHA-mediated glucose metabolism. The outcomes of this study elucidate the protective roles of IGF2BP3 in safeguarding vascular endothelial cells against injury.

Keywords: Glucose metabolism; HUVEC; IGF2BP3; LDHA; RNA binding protein; Vascular endothelial cell; ox-LDL.

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Conflict of interest statement

Compliance with Ethical Standards. Conflict of Interest: The authors declare no competing interests. Ethical Approval: This study was approved by the Ethics Committee of The First People’s Hospital of Linping District, Hangzhou City, China (#2021-088). Consent to Participate: Informed consent was obtained from all participants. Consent to Publish: All authors have read and agreed to publish this study.

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