源自华通氏胶间充质干细胞的细胞外基质通过整合素 αVβ3/c-Myc/P300/VEGF 促进血管生成。

Extracellular matrix derived from Wharton's Jelly-derived mesenchymal stem cells promotes angiogenesis via integrin αVβ3/c-Myc/P300/VEGF.

机构信息

Department of Clinical Laboratory, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, Shandong, China.

Department of Gastroenterology, Qilu Hospital of Shandong University, Jinan, 250012, Shandong, China.

出版信息

Stem Cell Res Ther. 2022 Jul 18;13(1):327. doi: 10.1186/s13287-022-03009-5.

DOI:10.1186/s13287-022-03009-5

PMID:35851415

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9290299/

Abstract

BACKGROUND

Angiogenesis is required in many physiological conditions, including bone regeneration, wound healing, and tissue regeneration. Mesenchymal stem cells-derived extracellular matrix (MSCs-ECM) could guide intricate cellular and tissue processes such as homeostasis, healing and regeneration.

METHODS

The purpose of this study is to explore the effect and mechanism of ECM derived from decellularized Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) on endothelial cell viability and angiogenesis. The human umbilical vein endothelial cells (HUVECs) were pretreated with WJ-MSCs ECM for 2d/7d/14d, respectively. After pretreatment, the angiogenesis ability of HUVECs was detected.

RESULTS

In this study, we found for the first time that WJ-MSCs ECM could improve the angiogenesis ability of HUVECs with a time-dependent manner in vitro. Mechanically, WJ-MSCs ECM activated the focal adhesion kinase (FAK)/P38 signaling pathway via integrin αVβ3, which further promoted the expression of the cellular (c)-Myc. Further, c-Myc increased histone acetylation levels of the vascular endothelial growth factor (VEGF) promoter by recruiting P300, which ultimately promoting VEGF expression.

CONCLUSIONS

ECM derived from Wharton's Jelly-derived mesenchymal stem cells promotes angiogenesis via integrin αVβ3/c-Myc/P300/VEGF. This study is expected to provide a new approach to promote angiogenesis in bone and tissue regeneration.

摘要

背景

血管生成是许多生理条件所必需的，包括骨再生、伤口愈合和组织再生。间充质干细胞衍生的细胞外基质（MSCs-ECM）可以指导复杂的细胞和组织过程，如稳态、愈合和再生。

方法

本研究旨在探讨去细胞化 Wharton 胶衍生间充质干细胞（WJ-MSCs）衍生的细胞外基质（ECM）对内皮细胞活力和血管生成的作用和机制。人脐静脉内皮细胞（HUVECs）分别用 WJ-MSCs ECM 预处理 2d/7d/14d。预处理后，检测 HUVECs 的血管生成能力。

结果

本研究首次发现，WJ-MSCs ECM 可以在体外以时间依赖性方式提高 HUVECs 的血管生成能力。从机制上讲，WJ-MSCs ECM 通过整合素 αVβ3 激活粘着斑激酶（FAK）/P38 信号通路，进而促进细胞（c）-Myc 的表达。此外，c-Myc 通过募集 P300 增加血管内皮生长因子（VEGF）启动子的组蛋白乙酰化水平，从而促进 VEGF 的表达。