PMID- 30038053 OWN - NLM STAT- MEDLINE DCOM- 20191025 LR - 20191025 IS - 1479-6813 (Electronic) IS - 0952-5041 (Linking) VI - 61 IP - 4 DP - 2018 Oct 15 TI - Dimethyl fumarate accelerates wound healing under diabetic condition. PG - 163-172 LID - JME-18-0102 [pii] LID - 10.1530/JME-18-0102 [doi] AB - Impaired wound healing is a common complication among patients with diabetes mellitus (DM), resulting in high rates of disability and mortality. Recent findings highlighted the critical role of nuclear factor erythroid 2-related factor 2 (NRF2) - a master of cellular antioxidants scavenging excessive DM-induced free radicals - in accelerating diabetic wound healing. Dimethyl fumarate (DMF) is a potent NRF2 activator used for the treatment of multiple sclerosis. However, the effect of DMF on wound healing has not been determined. The present study investigated the effect of DMF on the diabetic and the non-diabetic wound healing in streptozotocin-induced diabetic mice and non-diabetic control mice. DMF activated NRF2 signaling under both conditions. Interestingly, DMF attenuated oxidative damage and inflammation, and accelerated wound closure in the diabetic mice. However, this effect was not observed in non-diabetic mice. Keratinocytes were treated with normal glucose (NG), high glucose (HG), or hydrogen peroxide (H2O2), in the presence or absence of DMF to assess the role of reactive oxygen species (ROS) - inducible in DM - in mediating DMF-induced protection. Both HG and H2O2 elevated ROS, oxidative damage, and inflammation, the effects of which were similarly blunted by DMF. However, in spite of the activation of NRF2, DMF lost this capability under the NG condition. The findings of this study demonstrate that ROS activate the protective effect of DMF on the diabetic wound healing. FAU - Li, Ying AU - Li Y AD - Department of Dermatology, Affiliated Hospital of Beihua University, Jilin, Jilin, China. FAU - Ma, Fuzhe AU - Ma F AD - Department of Nephrology, The First Hospital of Jilin University, Changchun, Jilin, China. FAU - Li, Huimin AU - Li H AD - Department of Clinical Laboratory, The Second Hospital of Jilin University, Changchun, Jilin, China. FAU - Song, Yuguo AU - Song Y AD - Research Institute of Clinical Immunology, Affiliated Hospital of Beihua University, Jilin, Jilin, China. AD - Research Center for Life Sciences, Beihua University, Jilin, Jilin, China. FAU - Zhang, Huan AU - Zhang H AD - Operating Theater, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China. FAU - Jiang, Ziping AU - Jiang Z AD - Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, Jilin, China. FAU - Wu, Hao AU - Wu H AD - Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, Jilin, China. AD - Department of Translational Medicine, The First Hospital of Jilin University, Changchun, Jilin, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181015 PL - England TA - J Mol Endocrinol JT - Journal of molecular endocrinology JID - 8902617 RN - 0 (NF-E2-Related Factor 2) RN - 0 (Reactive Oxygen Species) RN - BBX060AN9V (Hydrogen Peroxide) RN - FO2303MNI2 (Dimethyl Fumarate) SB - IM MH - Animals MH - Diabetes Mellitus, Experimental/*drug therapy/*metabolism MH - Dimethyl Fumarate/*therapeutic use MH - Hydrogen Peroxide/pharmacology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - NF-E2-Related Factor 2/metabolism MH - Oxidative Stress/drug effects MH - Reactive Oxygen Species/metabolism MH - Signal Transduction/drug effects MH - Wound Healing/drug effects EDAT- 2018/07/25 06:00 MHDA- 2019/10/28 06:00 CRDT- 2018/07/25 06:00 PHST- 2018/07/23 00:00 [aheadofprint] PHST- 2018/04/23 00:00 [received] PHST- 2018/07/11 00:00 [revised] PHST- 2018/07/19 00:00 [accepted] PHST- 2018/07/25 06:00 [entrez] PHST- 2018/07/25 06:00 [pubmed] PHST- 2019/10/28 06:00 [medline] AID - JME-18-0102 [pii] AID - 10.1530/JME-18-0102 [doi] PST - epublish SO - J Mol Endocrinol. 2018 Oct 15;61(4):163-172. doi: 10.1530/JME-18-0102.