Hypoxia preconditioned DPSC-derived exosomes regulate angiogenesis via transferring LOXL2.

Abstract	Hypoxia was proved to enhance the angiogenesis of stem cells. However, the mechanism of the angiogenic potential in hypoxia-pretreated dental pulp stem cells (DPSCs) is poorly understood. We previously confirmed that hypoxia enhances the angiogenic potential of DPSC-derived exosomes with upregulation of lysyl oxidase-like 2 (LOXL2). Therefore, our study aimed to illuminate whether these exosomes promote angiogenesis via transfer of LOXL2. Exosomes were generated from hypoxia-pretreated DPSCs (Hypo-Exos) stably silencing LOXL2 after lentiviral transfection and characterized with transmission electron microscopy, nanosight and Western blot. The efficiency of silencing was verified using quantitative real-time PCR (qRT-PCR) and Western blot. CCK-8, scratch and transwell assays were conducted to explore the effects of LOXL2 silencing on DPSCs proliferation and migration. Human umbilical vein endothelial cells (HUVECs) were co-incubated with exosomes to assess the migration and angiogenic capacity through transwell and matrigel tube formation assays. The relative expression of angiogenesis-associated genes was characterized by qRT-PCR and Western blot. LOXL2 was successfully silenced in DPSCs and inhibited DPSC proliferation and migration. LOXL2 silencing in Hypo-Exos partially reduced promotion of HUVEC migration and tube formation and inhibited the expression of angiogenesis-associated genes. Thus, LOXL2 is one of various factors mediating the angiogenic effects of Hypo-Exos.
Authors	Baoyu Li, Ailin Liang, Yanling Zhou, Yihua Huang, Chenxi Liao, Xufang Zhang, Qimei Gong
Journal	Experimental cell research (Exp Cell Res) Vol. 425 Issue 2 Pg. 113543 (04 15 2023) ISSN: 1090-2422 [Electronic] United States
PMID	36894050 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2023 Elsevier Inc. All rights reserved.
Chemical References	LOXL2 protein, human Amino Acid Oxidoreductases
Topics	Humans Exosomes (metabolism) Cell Proliferation (genetics) Neovascularization, Physiologic (genetics) Human Umbilical Vein Endothelial Cells Stem Cells Amino Acid Oxidoreductases (genetics)

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