1,25(OH)(2)D-3 Strengthens the Vasculogenesis of Multipotent Mesenchymal Stromal Cells from Rat Bone Marrow by Regulating the PI3K/AKT Pathway

doi:10.2147/DDDT.S222244

科研成果详情

题名	1,25(OH)(2)D-3 Strengthens the Vasculogenesis of Multipotent Mesenchymal Stromal Cells from Rat Bone Marrow by Regulating the PI3K/AKT Pathway
作者	Ye, Bozhi1; Weng, Yawen 2; Lin, Shuang1; Lin, Jiahui3; Huang, Zhouqing1; Huang, Weijian1; Cai, Xueli1
发表日期	2020
发表期刊	DRUG DESIGN DEVELOPMENT AND THERAPY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	multipotent mesenchymal stromal cells 1,25(OH)(2)D-3 vasculogenesis vitamin D receptor PI3K/AKT pathway
其他关键词	ENDOTHELIAL GROWTH-FACTOR ; STEM-CELLS ; VITAMIN-D ; HYPOXIA ; VEGF ; DIFFERENTIATION ; PROLIFERATION ; PHENOTYPE ; SURVIVAL ; IMPROVES
摘要	Background: Multipotent mesenchymal stromal cells (MSCs) have recently been reported to promote vasculogenesis by differentiating into endothelial cells and releasing numerous cytokines and paracrine factors. However, due to low cell activity, their potential for clinical application is not very satisfactory. This study aimed to explore the effects and mechanisms of 1,25-dihydroxyvitamin D (1,25(OH)(2)D-3) on the vasculogenesis of MSCs. Methods: MSCs were isolated from the femurs and tibias of rats and characterized by flow cytometry. After treatment with different concentrations of 1,25(OH)(2)D-3 (0 mu M, 0.1 mu M and 1 mu M), the proliferation of MSCs was analyzed by Cell Counting Kit-8 (CCK-8), and the migratory capability was measured by Transwell assays and cell scratch tests. Capillary-like structure formation was observed by using Matrigel. Western blotting was used to detect the expression of FLK-1 and vWF to investigate the differentiation of MSCs into endothelial cells. Western blotting and gelatin zymography were used to detect the expression and activities of VEGF, MMP-2 and MMP-9 secreted by MSCs under the influence of 1,25(OH)(2)D-3 Finally, the VDR antagonist pyridoxal-5-phosphate (P5P) and the PI3K/AKT pathway inhibitor LY294002 were utilized to test the phosphorylation levels of key kinases in the PI3K/AKT pathway by Western blotting and the formation of capillary-like structures in Matrigel. Results: The proliferation and migratory capability of MSCs and the ability of MSCs to form a tube-like structure in Matrigel were enhanced after treatment with 1,25(OH)(2)D-3. Moreover, MSCs treated with 1,25(OH)(2)D-3 showed high expression of vWF and Flk-1. There was a significant increase in the expression of VEGF, MMP-2 and MMP-9 secreted by MSCs treated with 1,25(OH)(2)D-3, as well as in the activity of MMP-2 and MMP-9. The phosphorylation level of AKT increased with time after 1,25(OH)(2)D-3 treatment, while LY294002 weakened AKT phosphorylation. In addition, the ability to form capillary-like structures was reduced when the VDR and PI3K/AKT pathways were blocked. Conclusion: This study confirmed that 1,25(OH)(2)D-3 treatment can strengthen the ability of MSCs to promote vasculogenesis in vitro, and the mechanism may be related to the activation of the PI3K/AKT pathway.
资助项目	Wenzhou Science and Technology Bureau [Y20160030]
出版者	DOVE MEDICAL PRESS LTD
出版地	ALBANY
ISSN	1177-8881
卷号	14 页码:1157-1167
DOI	10.2147/DDDT.S222244
页数	11
WOS类目	Chemistry, Medicinal ; Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000521046200001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	32214801
PMC记录号	PMC7083642
SCOPUSEID	2-s2.0-85082486419
通讯作者地址	[Huang, Weijian]Department of Cardiology,The Key Lab of Cardiovascular Disease of Wenzhou,The First Affiliated Hospital of Wenzhou Medical University,2 Fuxue Road,Zhejiang,325000,China
Scopus学科分类	Pharmacology;Pharmaceutical Science;Drug Discovery
引用统计	被引频次：3[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/13631
专题	附属第一医院第一临床医学院（信息与工程学院）、附属第一医院附属第二医院第二临床医学院、附属第二医院、育英儿童医院第二临床医学院、附属第二医院、育英儿童医院_儿科学
通讯作者	Huang, Weijian
作者单位	1.Department of Cardiology,The Key Lab of Cardiovascular Disease of Wenzhou,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,China; 2.Department of Pediatrics,The Second School of Medicine,Wenzhou Medical University,Wenzhou,China; 3.The First School of Medicine,Wenzhou Medical University,Wenzhou,China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Ye, Bozhi,Weng, Yawen,Lin, Shuang,et al. 1,25(OH)(2)D-3 Strengthens the Vasculogenesis of Multipotent Mesenchymal Stromal Cells from Rat Bone Marrow by Regulating the PI3K/AKT Pathway[J]. DRUG DESIGN DEVELOPMENT AND THERAPY,2020,14:1157-1167.
APA	Ye, Bozhi., Weng, Yawen., Lin, Shuang., Lin, Jiahui., Huang, Zhouqing., ... & Cai, Xueli. (2020). 1,25(OH)(2)D-3 Strengthens the Vasculogenesis of Multipotent Mesenchymal Stromal Cells from Rat Bone Marrow by Regulating the PI3K/AKT Pathway. DRUG DESIGN DEVELOPMENT AND THERAPY, 14, 1157-1167.
MLA	Ye, Bozhi,et al."1,25(OH)(2)D-3 Strengthens the Vasculogenesis of Multipotent Mesenchymal Stromal Cells from Rat Bone Marrow by Regulating the PI3K/AKT Pathway".DRUG DESIGN DEVELOPMENT AND THERAPY 14(2020):1157-1167.