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Hypoxia endothelial cells-derived exosomes facilitate diabetic wound healing through improving endothelial cell function and promoting M2 macrophages polarization

Hypoxia endothelial cells-derived exosomes facilitate diabetic wound healing through improving endothelial cell function and promoting M2 macrophages polarization

Authors :
Peng Cheng
Xudong Xie
Liangcong Hu
Wu Zhou
Bobin Mi
Yuan Xiong
Hang Xue
Kunyu Zhang
Yuxiao Zhang
Yiqiang Hu
Lang Chen
Kangkang Zha
Bin Lv
Ze Lin
Chuanlu Lin
Guandong Dai
Yixin Hu
Tengbo Yu
Hankun Hu
Guohui Liu
Yingze Zhang
Source :
Bioactive Materials, Vol 33, Iss , Pp 157-173 (2024)
Publication Year :
2024
Publisher :
KeAi Communications Co., Ltd., 2024.

Abstract

It is imperative to develop and implement newer, more effective strategies to address refractory diabetic wounds. As of now, there is currently no optimal solution for these wounds. Hypoxic human umbilical vein endothelial cells (HUVECs)-derived exosomes have been postulated to promote diabetic wound healing, however, its effect and molecular mechanism need further study. In this study, we aimed to investigate whether hypoxic exosomes enhance wound healing in diabetics. Based on our high-throughput sequencing, differentially expressed lncRNAs (including 64 upregulated lncRNAs and 94 downregulated lncRNAs) were found in hypoxic exosomes compared to normoxic exosomes. Interestingly, lncHAR1B was one of the prominently upregulated lncRNAs in hypoxic exosomes, showing a notable correlation with diabetic wound healing. More specifically, hypoxic exosomes were transmitted to surrounding cells, which resulted in a significant increase in lncHAR1B level, thereby relieving the dysfunction of endothelial cells and promoting the switch from M1 to M2 macrophages under high glucose conditions. Mechanistically, lncHAR1B directly interacted with the transcription factor basic helix-loop-helix family member e23 (BHLHE23), which subsequently led to its binding to the KLF transcription factor 4 (KLF4) and promoted KLF4 expression. In our in vivo experiments, the use of hypoxic exosomes-loaded HGM-QCS hydrogels (Gel-H-Exos) resulted in rapid wound healing compared to that of normoxic exosomes-loaded HGM-QCS hydrogels (Gel-N-Exos) and diabetic groups. Consequently, our study provides potentially novel therapeutic approaches aimed at accelerating wound healing and developing a practical exosomes delivery platform.

Details

Language :
English
ISSN :
2452199X
Volume :
33
Issue :
157-173
Database :
Directory of Open Access Journals
Journal :
Bioactive Materials
Publication Type :
Academic Journal
Accession number :
edsdoj.0709a3d1a9a94507a6eec28f88c67afd
Document Type :
article
Full Text :
https://doi.org/10.1016/j.bioactmat.2023.10.020