Hypoxia macrophage-derived exosomal miR-26b-5p targeting PTEN promotes the development of keloids

Siya Dai; Mingyuan Xu; Qianqian Pang; Jiaqi Sun; Xiaohu Lin; Xi Chu; Chunyi Guo; Jinghong Xu

doi:10.1093/burnst/tkad036

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Hypoxia macrophage-derived exosomal miR-26b-5p targeting PTEN promotes the development of keloids

更新时间：2024-04-19

- Hypoxia macrophage-derived exosomal miR-26b-5p targeting PTEN promotes the development of keloids
- Burns & Trauma Vol. 12, Issue 1, (2024)
- 作者机构：
  
  1. Department of Plastic Surgery
  2. Zhejiang University
  3. Department of Plastic Surgery, Ningbo Second Hospital
  4. Department of Plastic and Reconstructive Surgery, Zhejiang Provincial People's Hospital
- 作者简介：
- 基金信息：
- DOI：10.1093/burnst/tkad036
  CLC：
- Published：2024，
  
  Published Online：29 February 2024，
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Siya Dai, Mingyuan Xu, Qianqian Pang, Jiaqi Sun, Xiaohu Lin, Xi Chu, Chunyi Guo, Jinghong Xu, Hypoxia macrophage-derived exosomal miR-26b-5p targeting PTEN promotes the development of keloids, Burns & Trauma, Volume 12, 2024, tkad036, https://doi.org/10.1093/burnst/tkad036
DOI：

Siya Dai, Mingyuan Xu, Qianqian Pang, Jiaqi Sun, Xiaohu Lin, Xi Chu, Chunyi Guo, Jinghong Xu, Hypoxia macrophage-derived exosomal miR-26b-5p targeting PTEN promotes the development of keloids, Burns & Trauma, Volume 12, 2024, tkad036, https://doi.org/10.1093/burnst/tkad036 DOI：

摘要

Abstract

BackgroundHypoxia is the typical characteristic of keloids. The development of keloids is closely related to the abnormal phenotypic transition of macrophages. However

the role of exosomal microRNAs (miRNAs) derived from hypoxic macrophages in keloids remains unclear. This study aimed to explore the role of hypoxic macrophage-derived exosomes (HMDE) in the occurrence and development of keloids and identify the critical miRNA.MethodsThe expression of CD206+ M2 macrophage in keloids and normal skin tissues was examined through immunofluorescence. The polarization of macrophages under a hypoxia environment was detected through flow cytometry. The internalization of macrophage-derived exosomes in human keloid fibroblasts (HKFs) was detected using a confocal microscope. miRNA sequencing was used to explore the differentially expressed miRNAs in exosomes derived from the normoxic and hypoxic macrophage. Subsequently

the dual-luciferase reporter assay verified that phosphatase and tension homolog (PTEN) was miR-26b-5p’s target. The biological function of macrophage-derived exosomes

miR-26b-5p and PTEN were detected using the CCK-8

wound-healing and Transwell assays. Western blot assay was used to confirm the miR-26b-5p’s underlying mechanisms and PTEN-PI3K/AKT pathway.ResultsWe demonstrated that M2-type macrophages were enriched in keloids and that hypoxia treatment could polarize macrophages toward M2-type. Compared with normoxic macrophages-derived exosomes (NMDE)

HMDE promote the proliferation

migration and invasion of HKFs. A total of 38 differential miRNAs (18 upregulated and 20 downregulated) were found between the NMDE and HMDE. miR-26b-5p was enriched in HMDE

which could be transmitted to HKFs. According to the results of the functional assay

exosomal miR-26b-5p produced by macrophages facilitated HKFs’ migration

invasion and proliferation via the PTEN-PI3K/AKT pathway.ConclusionsThe highly expressed miR-26b-5p in HMDE promotes the development of keloids via the PTEN-PI3K/AKT pathway.

关键词

Keywords

HypoxiaKeloidMacrophageExosomemiR-26b-5pPhosphatase and tension homolog

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