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Nrf2 Suppression Delays Diabetic Wound Healing Through Sustained Oxidative Stress and Inflammation

Nrf2 Suppression Delays Diabetic Wound Healing Through Sustained Oxidative Stress and Inflammation

Min Li, Haibing Yu, Haiyan Pan, Xueqing Zhou, Qiongfang Ruan, Danli Kong, Zhigang Chu, Huawen Li, Jingwen Huang, Xiaodong Huang, Angel Chau, Weiguo Xie, Yuanlin Ding, Paul Yao

Front Pharmacol. 2019 Sep 20;10:1099.

PMID: 31616304

Abstract:

Impaired wound healing is one of the major complications of diabetes, involving prolonged inflammation, delayed re-epithelialization, and consistent oxidative stress. The detailed mechanism remains unclear, and there is currently no effective treatment for diabetic wound healing. In this study, we aim to investigate the potential role and effect of nuclear factor erythroid-2-related factor-2 (Nrf2) activation on diabetic wound healing. In vitro experiments in rat macrophages showed that hyperglycemia treatment suppresses Nrf2 activation, resulting in oxidative stress with decreased expression of antioxidant genes, including NAD(P)H:quinone oxidoreductase 1 and heme oxygenase 1, together with increased secretion of proinflammatory cytokines, including interleukin 1β (IL1β), IL6, and monocyte chemoattractant protein-1. Both Nrf2 overexpression and Nrf2 activator dimethyl fumarate (DMF) treatment significantly ameliorated oxidative stress and inflammation. On the other hand, both Nrf2 knockdown or Nrf2 inhibitor ML385 mimicked the effect of diabetes. Further in vivo experiments in rats showed that DMF treatment significantly accelerated wound healing in streptozocin-induced diabetic rats with increased expression of antioxidant enzymes and decreased secretion of proinflammatory cytokines, while Nrf2 inhibitor ML385 mimicked the effect of diabetes. We conclude that Nrf2 activation accelerates impaired wound healing by ameliorating diabetes-mediated oxidative stress and inflammation. This provides a new clinical treatment strategy for diabetic wound healing using Nrf2 activator DMF.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP846557719	ML385		846557-71-9	Price

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