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https://hdl.handle.net/2440/121151
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Type: | Journal article |
Title: | Hypoxia-inducible factor-1α (HIF-1α) potentiates β-cell survival after islet transplantation of human and mouse islets |
Other Titles: | Hypoxia-inducible factor-1alpha (HIF-1alpha) potentiates beta-cell survival after islet transplantation of human and mouse islets |
Author: | Stokes, R.A. Cheng, K. Deters, N. Lau, S.M. Hawthorne, W.J. O'Connell, P.J. Stolp, J. Grey, S. Loudovaris, T. Kay, T.W. Thomas, H.E. Gonzalez, F.J. Gunton, J.E. |
Citation: | Cell Transplantation, 2013; 22(2):259-266 |
Publisher: | SAGE Publications |
Issue Date: | 2013 |
ISSN: | 0963-6897 1555-3892 |
Statement of Responsibility: | Rebecca A. Stokes, Kim Cheng, Natasha Deters, Sue Mei Lau, Wayne J. Hawthorne ... Shane Grey ... et al. |
Abstract: | A high proportion of β-cells die within days of islet transplantation. Reports suggest that induction of hypoxia-inducible factor-1α (HIF-1α) predicts adverse transplant outcomes. We hypothesized that this was a compensatory response and that HIF-1α protects β-cells during transplantation. Transplants were performed using human islets or murine β-cell-specific HIF-1α-null (β-HIF-1α-null) islets with or without treatment with deferoxamine (DFO) to increase HIF-1α. β-HIF-1α-null transplants had poor outcomes, demonstrating that lack of HIF-1α impaired transplant efficiency. Increasing HIF-1α improved outcomes for mouse and human islets. No effect was seen in β-HIF-1α-null islets. The mechanism was decreased apoptosis, resulting in increased β-cell mass posttransplantation. These findings show that HIF-1α is a protective factor and is required for successful islet transplant outcomes. Iron chelation with DFO markedly improved transplant success in a HIF-1α-dependent manner, thus demonstrating the mechanism of action. DFO, approved for human use, may have a therapeutic role in the setting of human islet transplantation. |
Keywords: | Hypoxia-inducible factor-1α (HIF-1α), β-Cell function, islet transplantation; deferoxamine (DFO); diabetes; hypoxia |
Rights: | © 2013 Cognizant Comm. Corp. |
DOI: | 10.3727/096368912X647180 |
Published version: | http://dx.doi.org/10.3727/096368912x647180 |
Appears in Collections: | Animal and Veterinary Sciences publications Aurora harvest 8 |
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