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脂肪干细胞来源的外泌体通过 miR-146a-5p/JAZF1 轴增强糖尿病创面血管生成。

Exosomes Derived from Adipose Stem Cells Enhance Angiogenesis in Diabetic Wound Via miR-146a-5p/JAZF1 Axis.

机构信息

Department of Plastic and Reconstructive, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.

出版信息

Stem Cell Rev Rep. 2024 May;20(4):1026-1039. doi: 10.1007/s12015-024-10685-8. Epub 2024 Feb 23.

Abstract

Chronic trauma in diabetes is a leading cause of disability and mortality. Exosomes show promise in tissue regeneration. This study investigates the role of exosomes derived from adipose stem cells (ADSC-Exos) in angiogenesis. MiRNA-seq analysis revealed significant changes in 47 genes in human umbilical vein endothelial cells (HUVECs) treated with ADSC-Exos, with miR-146a-5p highly expressed. MiR-146a-5p mimics enhanced the pro-angiogenic effects of ADSC-Exos, while inhibitors had the opposite effect. JAZF1 was identified as a direct downstream target of miR-146a-5p through bioinformatics, qRT-PCR, and dual luciferase assay. Overexpress of JAZF1 resulted in decreased proliferation, migration, and angiogenic capacity of HUVECs, and reduced VEGFA expression. This study proposes that ADSC-Exos regulate angiogenesis partly via the miR-146a-5p/JAZF1 axis.

摘要

糖尿病慢性创伤是导致残疾和死亡的主要原因。外泌体在组织再生方面显示出前景。本研究探讨了来源于脂肪干细胞(ADSC-Exos)的外泌体在血管生成中的作用。miRNA-seq 分析显示,人脐静脉内皮细胞(HUVECs)用 ADSC-Exos 处理后有 47 个基因发生显著变化,miR-146a-5p 高表达。miR-146a-5p 模拟物增强了 ADSC-Exos 的促血管生成作用,而抑制剂则有相反的作用。通过生物信息学、qRT-PCR 和双荧光素酶测定,鉴定出 JAZF1 是 miR-146a-5p 的直接下游靶基因。JAZF1 的过表达导致 HUVECs 的增殖、迁移和血管生成能力下降,VEGFA 表达减少。本研究提出 ADSC-Exos 通过 miR-146a-5p/JAZF1 轴部分调节血管生成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8f37/11087353/c6922125235e/12015_2024_10685_Fig1_HTML.jpg

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