The long noncoding RNA PDK1‐AS/miR‐125b‐5p/VEGFA axis modulates human dermal microvascular endothelial cell and human umbilical vein endothelial cell angiogenesis after thermal injury. Issue 4 (20th October 2020)

• Record Type: Journal Article
• Authors: Zhou, Situo; Liang, Pengfei; Zhang, Pihong; Zhang, Minghua; Huang, Xiaoyuan
• Is Part Of: Journal of cellular physiology. Volume 236:Issue 4(2021)
• Page Start: 3129
• Page End: 3142
• Publication Date: 2020-10-20
• Subjects: angiogenesis -- human dermal microvascular endothelial cells (HDMECs) -- human umbilical vein endothelial cells (HUVECs) -- RNA PDK1‐AS/miR‐125b‐5p/VEGFA axis -- thermal injury; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.30081
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Our previous study confirmed the critical role of miR‐125b and vascular endothelial growth factor (VEGF) in burn wound repair., The present study was aimed to identify the role of long noncoding RNAs (lncRNAs) related to the function of miR‐125b and VEGF in burn wound repair and the underlying mechanism. First, we found that lncRNA PDK1‐AS and VEGFA expression was significantly increased in heat‐denatured dermal tissue samples and in human dermal microvascular endothelial cells (HDMECs) and human umbilical vein endothelial cells (HUVECs) after thermal injury. PDK1‐AS knockdown significantly inhibited cell viability, cumulative tube length, cell migratory ability, and cell invasion of thermally injured HDMECs and HUVECs. PDK1‐AS knockdown decreased VEGFA protein levels in HDMECs and HUVECs. While overexpression of PDK1‐AS showed the opposite effects. Online tools prediction and luciferase assay confirmed that miR‐125b‐5p targeted PDK1‐AS and VEGFA 3′‐untranslated region. miR‐125b‐5p inhibition significantly increased VEGFA protein levels and enhanced viability, cumulative tube length, migratory ability, and invasion of HUVECs and HDMECs. Furthermore, the effects of PDK1‐AS knockdown on VEGFA protein levels in the two cell lines were partially reversed by miR‐125b‐5p inhibition. Finally, in the tissue samples, PDK1‐AS and VEGFA expression was increased, while miR‐125b‐5p expression was decreased in heat‐denatured dermal tissues; the expression of miR‐125b‐5p had a negative correlation with PDK1‐AS and VEGFA, respectively, and PDK1‐AS and VEGFA were positively correlated with each other in tissue samples. In conclusion, PDK1‐AS relieves miR‐125b‐5p‐induced inhibition on VEGFA by acting as a endogenous RNA, therefore modulating HDMEC and HUVEC angiogenesis after thermal injury. Abstract : PDK1‐AS relieves miR‐125b‐5p‐induced inhibition on vascular endothelial growth factor by acting as a endogenous RNA, therefore modulating human dermal microvascular endothelial cel and human umbilical vein endothelial cell angiogenesis after thermal injury.