linc00174-EZH2-ZNF24/Runx1-VEGFA Regulatory Mechanism Modulates Post-burn Wound Healing

Mitao Huang; Xu Huang; Bimei Jiang; Pihong Zhang; Le Guo; Xu Cui; Situo Zhou; Licheng Ren; Minghua Zhang; Jizhang Zeng; Xiaoyuan Huang; Pengfei Liang

Molecular Therapy: Nucleic Acids (Sep 2020)

linc00174-EZH2-ZNF24/Runx1-VEGFA Regulatory Mechanism Modulates Post-burn Wound Healing

Mitao Huang,
Xu Huang,
Bimei Jiang,
Pihong Zhang,
Le Guo,
Xu Cui,
Situo Zhou,
Licheng Ren,
Minghua Zhang,
Jizhang Zeng,
Xiaoyuan Huang,
Pengfei Liang

Affiliations

Mitao Huang: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China
Xu Huang: Department of Hyperbaric Oxygen, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China
Bimei Jiang: Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha 410008, Hunan Province, P.R. China
Pihong Zhang: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China
Le Guo: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China
Xu Cui: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China
Situo Zhou: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China
Licheng Ren: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China
Minghua Zhang: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China
Jizhang Zeng: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China
Xiaoyuan Huang: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China
Pengfei Liang: Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, P.R. China; Corresponding author: Pengfei Liang, PhD, Department of Burns and Plastic Surgery, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Changsha 410008, Hunan Province, P.R. China.

Journal volume & issue: Vol. 21
pp. 824 – 836

Abstract

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Preservation of denatured dermis exerts promotive functions in wound healing and improves the appearance and function of skin. Angiogenesis is crucial for wound healing during burn injury. However, the potential molecular mechanism of angiogenesis in the recovery after burn injury remains to be elucidated. Herein, RNA chromatin immunoprecipitation (ChIP) sequencing analysis revealed upregulation of long intergenic non-coding RNA 00174 (linc00174) in the post-burn tissues. linc00174 overexpression promoted angiogenic activities of human umbilical vein endothelial cells (HUVECs) in the heat-denatured cell model, characterized by the promotion of cell proliferation, migration, and tube formation. Mechanistically, linc00174 directly bound to enhancer of zeste homolog 2 (EZH2), thus stimulating the protein level of trimethylation at lysine 27 of histone H3 (H3K27me3). Moreover, inhibition of EZH2 resulted in downregulation of ZNF24 and Runx1, as well as a decline of vascular endothelial growth factor A (VEGFA). Furthermore, EZH2 modulated epigenetic repression of ZNF24 and Runx1 through the promoter of H3K27me3. Additionally, ZNF24 and Runx1 both functioned as transcriptional inhibitors of VEGFA. Taken together, these findings uncover that linc00174 epigenetically inhibits ZNF24 and Runx1 expression through binding to EZH2, thus attenuating the suppression of VEGFA, contributing to the facilitation of angiogenesis during the recovery of heat-denatured endothelial cells.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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