Heparanase released from mesenchymal stem cells activates integrin beta1/HIF-2alpha/Flk-1 signaling and promotes endothelial cell migration and angiogenesis

Stem Cells
Xin-Yang HuJian'an Wang

Abstract

Heparanase plays important roles in tumor angiogenesis. Our previous study demonstrated that hypoxic preconditioning (HPC) enhanced the angiogenic and therapeutic effects of mesenchymal stem cells (MSCs), effects that were paralleled by enhanced heparanase expression. This study was designed to elucidate the role of heparanase in the improved therapeutic properties of HPC-MSCs and to explore underlying mechanisms using an ischemic rat hind limb model. MSCs transfected with heparanase (MSC(hpa) ) or empty vector (MSC(null) ) were delivered by intramuscular injections to ischemic hind limbs. Hind limbs that received MSC(hpa) recovered blood flow more rapidly at 7 days and acquired higher capillary density at 14 days compared with MSC(null) . Conditioned medium from MSC(hpa) increased endothelial cell migration and promoted greater tube formation relative to that from the MSC(null) groups. Vascular endothelial growth factor receptor 2 (VEGFR2, Flk-1) and its downstream signaling pathway (p38MAPK/HSP27) were significantly increased in human umbilical vein endothelial cells (HUVECs) after treatment with MSC(hpa) conditioned medium. Each of these responses was decreased by cocultured with MSC(hpa-KD) conditioned medium. MSC(hpa) cond...Continue Reading

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Citations

Apr 9, 2016·Future Medicinal Chemistry·Silvia RivaraGiuseppe Giannini
Aug 28, 2016·Biochimica Et Biophysica Acta·Sheng-An SuMeixiang Xiang
Oct 1, 2017·Circulation Research·Jun JiangJian'an Wang
Feb 20, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Tengfei ZhaoKan Xu
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Dec 19, 2019·Frontiers in Oncology·Deirdre R Coombe, Neha S Gandhi
Dec 2, 2020·Journal of Translational Medicine·Krishnath M Jayatilleke, Mark D Hulett

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Methods Mentioned

BETA
amputation
flow cytometry
scraping
Immunoprecipitation-PCR
immunoprecipitation
ChIP
PCR
Transfection
Assay
fluorescence microscopy

Software Mentioned

SPSS
image proplus
Pro Plus
Image

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