The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.
The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissues
Open accessAbstract
Diabetes is associated with poor outcomes following acute vascular occlusive events. This results in part from a failure to form adequate compensatory microvasculature in response to ischemia. Since vascular endothelial growth factor (VEGF) is an essential mediator of neovascularization, we examined whether hypoxic up-regulation of VEGF was impaired in diabetes. Both fibroblasts isolated from type 2 diabetic patients, and normal fibroblasts exposed chronically to high glucose, were defective in their capacity to up-regulate VEGF in response to hypoxia. In vivo, diabetic animals demonstrated an impaired ability to increase VEGF production in response to soft tissue ischemia. This resulted from a high glucose-induced decrease in transactivation by the transcription factor hypoxia-inducible factor-1α (HIF-1α), which mediates hypoxia-stimulated VEGF expression. Decreased HIF-1α functional activity was specifically caused by impaired HIF-1α binding to the coactivator p300. We identify covalent modification of p300 by the dicarbonyl metabolite methylglyoxal as being responsible for this decreased association. Administration of deferoxamine abrogated methylglyoxal conjugation, normalizing both HIF-1α/p300 interaction and transactivation by HIF-1α. In diabetic mice, deferoxamine promoted neovascularization and enhanced wound healing. These findings define molecular defects that underlie impaired VEGF production in diabetic tissues and offer a promising direction for therapeutic intervention.
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Cites
Biochemistry and molecular cell biology of diabetic complications
Brownlee, M. (2001) · Nature · doi:10.1038/414813a · Cited by 9,107
Self-citationActivation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
Forsythe, J. A., Jiang, B.-H., Iyer, N. V., Agani, F., Leung, S. W., Koos, R. D., & Semenza, G. L. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.4604 · Cited by 3,981
Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1
Ceradini, D. J., Kulkarni, A. R., Callaghan, M. J., Tepper, O. M., Bastidas, N., Kleinman, M. E., Capla, J. M., Galiano, R. D., Levine, J. P., & Gurtner, G. C. (2004) · Nature Medicine · doi:10.1038/nm1075 · Cited by 2,600
Self-citationOxygen sensing by HIF hydroxylases
Schofield, C. J., & Ratcliffe, P. J. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1366 · Cited by 2,068 · cited 1×
“This effect was not observed with the addition of dimethyloxalylglycine (DMOG), a competitive inhibitor of several enzymes involved in HIF-1 degradation (26).”
BackgroundNorhammar, A., Tenerz, Å., Nilsson, G., Hamsten, A., Efendíc, S., Rydén, L., & Malmberg, K. (2002) · The Lancet · doi:10.1016/s0140-6736(02)09089-x · Cited by 1,112
Appelhoff, R. J., Tian, Y.-M., Raval, R. R., Turley, H., Harris, A. L., Pugh, C. W., Ratcliffe, P. J., & Gleadle, J. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406026200 · Cited by 1,108
Stabilization of HIF-1α is critical to improve wound healing in diabetic mice
Botusan, I. R., Sunkari, V. G., Savu, O., Catrina, A. I., Grünler, J., Lindberg, S., Pereira, T., Ylä-Herttuala, S., Poellinger, L., Brismar, K., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805230105 · Cited by 533
Ahmed, N., & Thornalley, P. J. (2003) · Biochemical Society Transactions · doi:10.1042/bst0311417 · Cited by 152
Cited by
Oxidative stress and diabetic complications
Giacco, F., & Brownlee, M. (2010) · Circulation Research · doi:10.1161/circresaha.110.223545 · Cited by 5,461
Self-citationHypoxia-inducible factors in physiology and medicine
Semenza, G. L. (2012) · Cell · doi:10.1016/j.cell.2012.01.021 · Cited by 3,645
Wound Healing: A Cellular Perspective
Rodrigues, M., Kosaric, N., Bonham, C. A., & Gurtner, G. C. (2019) · Physiological Reviews · doi:10.1152/physrev.00067.2017 · Cited by 3,013
Self-citationOxygen Sensing, Hypoxia-Inducible Factors, and Disease Pathophysiology
Semenza, G. L. (2014) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104720 · Cited by 1,159
Schalkwijk, C. G., & Stehouwer, C. D. A. (2020) · Physiological Reviews · doi:10.1152/physrev.00001.2019 · Cited by 622
Metadata
- Authors
- Thangarajah, H., Yao, D., Chang, E. I., Shi, Y., Jazayeri, L., Vial, I. N., Galiano, R. D., Du, X.-L., Grogan, R., Galvez, M. G., Januszyk, M., Brownlee, M., & Gurtner, G. C.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-08-11
- Volume
- 106
- Issue
- 32
- Pages
- 13505-13510
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2170525767
- Cited by
- 464
- References
- 8
- FWCI
- 6.84
- Type
- journal article
- Language
- en
- Open access
- green
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- Thangarajah, H., Yao, D., Chang, E. I., Shi, Y., Jazayeri, L., Vial, I. N., Galiano, R. D., Du, X.-L., Grogan, R., Galvez, M. G., Januszyk, M., Brownlee, M., & Gurtner, G. C. (2009). The molecular basis for impaired hypoxia-induced VEGF expression in diabetic tissues. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0906670106
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