Hypoxia Inducible Factor-1α Regulates the Migration of Bone Marrow Mesenchymal Stem Cells via Integrin α 4

Stem Cells International
Jong Ho ChoiGi Jin Kim

Abstract

Although hypoxic environments have been known to regulate the migratory ability of bone marrow-derived mesenchymal stem cells (BM-MSCs), which is a critical factor for maximizing the therapeutic effect, the underlying mechanisms remain unclear. Therefore, we aimed to confirm the effect of hypoxia-inducible factor-1α (HIF-1α) on the migration of BM-MSCs and to analyze the interaction between HIF-1α and integrin-mediated signals. Hypoxia-activated HIF-1α significantly increased BM-MSC migration. The expression of integrin α 4 was decreased in BM-MSCs by increased HIF-1α under hypoxia, whereas the expression of Rho-associated kinase 1 (ROCK1) and Rac1/2/3 was increased. After downregulation of HIF-1α by YC-1, which is an inhibitor of HIF-1α, BM-MSC migration was decreased via upregulation of integrin α 4 and downregulation of ROCK1 and Rac1/2/3. Knockdown of integrin α 4 by integrin α 4 siRNA (siITGA4) treatment increased BM-MSC migration by upregulation of ROCK1, Rac1/2/3, and matrix metalloproteinase-2 regardless of oxygen tension. Moreover, siITGA4 treatment increased HIF-1α expression and augmented the translocation of HIF-1α into the nucleus under hypoxia. Taken together, the alternative expression of HIF-1α induced by microe...Continue Reading

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May 27, 2017·Translational Stroke Research·Oh Young BangUNKNOWN STARTING-2 trial investigators
Dec 19, 2016·European Journal of Cell Biology·Sajjad SisakhtnezhadHassan Akrami
Feb 13, 2019·Journal of Cell Science·Lewis S C WardHelen M McGettrick
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Dec 31, 2019·Journal of Oncology·Silvia BatistaBruno Costa-Silva
Apr 16, 2021·Advanced Science·Anna AndrzejewskaMiroslaw Janowski

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Methods Mentioned

BETA
GTPase
GTPases
PCR
electrophoresis
transfection

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