Hypoxia Inducible Factor-1α Regulates the Migration of Bone Marrow Mesenchymal Stem Cells via Integrin α4
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-in...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2016/7932185 |
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| author | Jong Ho Choi Yun Bin Lee Jieun Jung Seong Gyu Hwang IL-Hoan Oh Gi Jin Kim |
| author_facet | Jong Ho Choi Yun Bin Lee Jieun Jung Seong Gyu Hwang IL-Hoan Oh Gi Jin Kim |
| author_sort | Jong Ho Choi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-78827aae89404f1ca39456a48f550b9e |
| institution | Kabale University |
| issn | 1687-966X 1687-9678 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
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| series | Stem Cells International |
| spelling | doaj-art-78827aae89404f1ca39456a48f550b9e2025-02-03T01:30:05ZengWileyStem Cells International1687-966X1687-96782016-01-01201610.1155/2016/79321857932185Hypoxia Inducible Factor-1α Regulates the Migration of Bone Marrow Mesenchymal Stem Cells via Integrin α4Jong Ho Choi0Yun Bin Lee1Jieun Jung2Seong Gyu Hwang3IL-Hoan Oh4Gi Jin Kim5Department of Biomedical Science, CHA University, Seongnam-si 13488, Republic of KoreaDepartment of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 13496, Republic of KoreaDepartment of Nanobiomedical Science, Dankook University, Cheonan-si 31116, Republic of KoreaDepartment of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam-si 13496, Republic of KoreaCatholic High Performance Cell Therapy Center, The Catholic University of Korea, Seoul 06591, Republic of KoreaDepartment of Biomedical Science, CHA University, Seongnam-si 13488, Republic of KoreaAlthough 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.http://dx.doi.org/10.1155/2016/7932185 |
| spellingShingle | Jong Ho Choi Yun Bin Lee Jieun Jung Seong Gyu Hwang IL-Hoan Oh Gi Jin Kim Hypoxia Inducible Factor-1α Regulates the Migration of Bone Marrow Mesenchymal Stem Cells via Integrin α4 Stem Cells International |
| title | Hypoxia Inducible Factor-1α Regulates the Migration of Bone Marrow Mesenchymal Stem Cells via Integrin α4 |
| title_full | Hypoxia Inducible Factor-1α Regulates the Migration of Bone Marrow Mesenchymal Stem Cells via Integrin α4 |
| title_fullStr | Hypoxia Inducible Factor-1α Regulates the Migration of Bone Marrow Mesenchymal Stem Cells via Integrin α4 |
| title_full_unstemmed | Hypoxia Inducible Factor-1α Regulates the Migration of Bone Marrow Mesenchymal Stem Cells via Integrin α4 |
| title_short | Hypoxia Inducible Factor-1α Regulates the Migration of Bone Marrow Mesenchymal Stem Cells via Integrin α4 |
| title_sort | hypoxia inducible factor 1α regulates the migration of bone marrow mesenchymal stem cells via integrin α4 |
| url | http://dx.doi.org/10.1155/2016/7932185 |
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