Mesenchymal Stem Cell Migration and Proliferation Are Mediated by Hypoxia-Inducible Factor-1α Upstream of Notch and SUMO Pathways

Stem Cells and Development
María CiriaPilar Sepúlveda

Abstract

Mesenchymal stem cells (MSCs) are effective in treating several pathologies. We and others have demonstrated that hypoxia or hypoxia-inducible factor 1 alpha (HIF-1α) stabilization improves several MSC functions, including cell adhesion, migration, and proliferation, thereby increasing their therapeutic potential. To further explore the mechanisms induced by HIF-1α in MSCs, we studied its relationship with Notch signaling and observed that overexpression of HIF-1α in MSCs increased protein levels of the Notch ligands Jagged 1-2 and Delta-like (Dll)1, Dll3, and Dll4 and potentiated Notch signaling only when this pathway was activated. Crosstalk between HIF and Notch resulted in Notch-dependent migration and spreading of MSCs, which was abolished by γ-secretase inhibition. However, the HIF-1-induced increase in MSC proliferation was independent of Notch signaling. The ubiquitin family member, small ubiquitin-like modifier (SUMO), has important functions in many cellular processes and increased SUMO1 protein levels have been reported in hypoxia. To investigate the potential involvement of SUMOylation in HIF/Notch crosstalk, we measured general SUMOylation levels and observed increased SUMOylation in HIF-1-expressing MSCs. Moreover...Continue Reading

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Citations

Feb 1, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Dun Xian TanRussel J Reiter
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Sep 15, 2021·Proceedings of the National Academy of Sciences of the United States of America·Arushi JaiswalMichael Reedijk

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Methods Mentioned

BETA
flow cytometry
transfection
flow
PCR
Protein Assay
electrophoresis
immunoprecipitation
nuclear translocation
confocal microscopy

Software Mentioned

InCell
GraphPad Prism
InCell Analyzer 1000 Workstation
[UNK] Analysis
ImageJ
InCell Analyzer

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