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- Title
Dynamic production of hypoxia-inducible factor-1alpha in early transplanted islets.
- Authors
Miao, G; Ostrowski, R P; Mace, J; Hough, J; Hopper, A; Peverini, R; Chinnock, R; Zhang, J; Hathout, E
- Abstract
More than half of transplanted beta-cells undergo apoptotic cell death triggered by nonimmunological factors within a few days after transplantation. To investigate the dynamic hypoxic responses in early transplanted islets, syngeneic islets were transplanted under the kidney capsule of balb/c mice. Hypoxia-inducible factor-1alpha (HIF-1alpha) was strongly expressed at post-transplant day (POD) 1, increased on POD 3, and gradually diminished on POD 14. Insulin secretion decreased on POD 3 in association with a significant increase of HIF-1alpha-related beta-cell death, which can be suppressed by short-term hyperbaric oxygen therapy. On POD 7, apoptosis was not further activated by continually produced HIF-1alpha. In contrast, improvement of nerve growth factor and duodenal homeobox factor-1 (PDx-1) production resulted in islet graft recovery and remodeling. In addition, significant activation of vascular endothelial growth factor in islet grafts on POD 7 correlated with development of massive newly formed microvessels, whose maturation is advanced on POD 14 with gradual diminution of HIF-1alpha. We conclude that (1) transplanted islets strongly express HIF-1alpha in association with beta-cell death and decreased insulin production until adequate revascularization is established and (2) early suppression of HIF-1alpha results in less beta-cell death thereby minimizing early graft failure.
- Publication
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2006, Vol 6, Issue 11, p2636
- ISSN
1600-6135
- Publication type
Journal Article
- DOI
10.1111/j.1600-6143.2006.01541.x