Hypoxia Inducible Factor‐1α Regulates the Migration of Bone Marrow Mesenchymal Stem Cells via Integrin α4

• DOI: 10.1155/2016/7932185
• Publication Date: 2016-01-04T21:02:29Z
• Authors: Jong Ho Choi; Yun Bin Lee; Jieun Jung; Seong Gyu Hwang; IL-Hoan Oh; Gi Jin Kim
• Keywords: 0303 health sciences; 03 medical and health sciences; Internal medicine; RC31-1245; Research Article; 3. Good health

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 α4 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 α4 and downregulation of ROCK1 and Rac1/2/3. Knockdown of integrin α4 by integrin α4 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 microenvironment factors, such as hypoxia and integrin α4, may regulate the migration of BM‐MSCs. These findings may provide insights to the underlying mechanisms of BM‐MSC migration for successful stem cell‐based therapy.