The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
An Essential Role of NRF2 in Diabetic Wound Healing
Open accessAbstract
The high mortality and disability of diabetic nonhealing skin ulcers create an urgent need for the development of more efficacious strategies targeting diabetic wound healing. In the current study, using human clinical specimens, we show that perilesional skin tissues from patients with diabetes are under more severe oxidative stress and display higher activation of the nuclear factor-E2–related factor 2 (NRF2)–mediated antioxidant response than perilesional skin tissues from normoglycemic patients. In a streptozotocin-induced diabetes mouse model, Nrf2−/− mice have delayed wound closure rates compared with Nrf2+/+ mice, which is, at least partially, due to greater oxidative DNA damage, low transforming growth factor-β1 (TGF-β1) and high matrix metalloproteinase 9 (MMP9) expression, and increased apoptosis. More importantly, pharmacological activation of the NRF2 pathway significantly improves diabetic wound healing. In vitro experiments in human immortalized keratinocyte cells confirm that NRF2 contributes to wound healing by alleviating oxidative stress, increasing proliferation and migration, decreasing apoptosis, and increasing the expression of TGF-β1 and lowering MMP9 under high-glucose conditions. This study indicates an essential role for NRF2 in diabetic wound healing and the therapeutic benefits of activating NRF2 in this disease, laying the foundation for future clinical trials using NRF2 activators in treating diabetic skin ulcers.
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Cites
Gurtner, G. C., Werner, S., Barrandon, Y., & Longaker, M. T. (2008) · Nature · doi:10.1038/nature07039 · Cited by 6,542
Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway
Kensler, T. W., Wakabayashi, N., & Biswal, S. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.46.120604.141046 · Cited by 3,630
The molecular biology of chronic wounds and delayed healing in diabetes
Blakytny, R., & Jude, E. (2006) · Diabetic Medicine · doi:10.1111/j.1464-5491.2006.01773.x · Cited by 632
Therapeutic Potential of Nrf2 Activators in Streptozotocin-Induced Diabetic Nephropathy
Zheng, H., Whitman, S. A., Wu, W., Wondrak, G. T., Wong, P. K., Fang, D., & Zhang, D. D. (2011) · Diabetes · doi:10.2337/db11-0807 · Cited by 507
Self-citationBraun, S., Hanselmann, C., Gassmann, M. G., auf dem Keller, U., Born-Berclaz, C., Chan, K., Kan, Y. W., & Werner, S. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.15.5492-5505.2002 · Cited by 410
Cited by
NRF2 and the Hallmarks of Cancer
Rojo de la Vega, M., Chapman, E., & Zhang, D. D. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.022 · Cited by 1,672
Self-citationThirty years of NRF2: advances and therapeutic challenges.
Zhang, D. D. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01145-0 · Cited by 282
Self-citationRojo de la Vega, M., Krajisnik, A., Zhang, D., & Wondrak, G. (2017) · Nutrients · doi:10.3390/nu9121371 · Cited by 77
Self-citationTopical bixin confers NRF2-dependent protection against photodamage and hair graying in mouse skin
Rojo de la Vega, M., Zhang, D. D., & Wondrak, G. T. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00287 · Cited by 55
Self-citationThe management of diabetes mellitus by mangiferin: advances and prospects
Wang, M., Liang, Y., Chen, K., Wang, M., Long, X., Liu, H., Sun, Y., & He, B. (2022) · Nanoscale · doi:10.1039/d1nr06690k · Cited by 56
Metadata
- Authors
- Long, M., Rojo de la Vega, M., Wen, Q., Bharara, M., Jiang, T., Zhang, R., Zhou, S., Wong, P. K., Wondrak, G. T., Zheng, H., & Zhang, D. D.
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2015-12-30
- Volume
- 65
- Issue
- 3
- Pages
- 780-793
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2201268631
- Cited by
- 265
- References
- 5
- FWCI
- 12.74
- Type
- journal article
- Language
- en
- Open access
- bronze
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