Hypoxia Inducible Factor-1α Regulates the Migration of Bone Marrow Mesenchymal Stem Cells via Integrin α4. (4th January 2016)

• Record Type: Journal Article
• Authors: Choi, Jong Ho; Lee, Yun Bin; Jung, Jieun; Hwang, Seong Gyu; Oh, IL-Hoan; Kim, Gi Jin
• Other Names: Li Tao-Sheng Academic Editor.
• Is Part Of: Stem cells international. Volume 2016(2016)
• Publication Date: 2016-01-04
• Subjects: Stem Cells -- Periodicals; Stem Cells -- Therapeutic use -- Periodicals; Stem Cells -- Transplantation -- Periodicals; 616.0277405
• DOI: 10.1155/2016/7932185
• Languages: English
• ISSNs: 1687-966X

Abstract

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-1 α (HIF-1 α ) on the migration of BM-MSCs and to analyze the interaction between HIF-1 α and integrin-mediated signals. Hypoxia-activated HIF-1 α significantly increased BM-MSC migration. The expression of integrin α 4 was decreased in BM-MSCs by increased HIF-1 α under hypoxia, whereas the expression of Rho-associated kinase 1 (ROCK1) and Rac1/2/3 was increased. After downregulation of HIF-1 α by YC-1, which is an inhibitor of HIF-1 α, 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-1 α expression and augmented the translocation of HIF-1 α into the nucleus under hypoxia. Taken together, the alternative expression of HIF-1 α induced by microenvironment factors, such as hypoxia and integrin α 4, 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.