Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6156074 | Translational Research | 2016 | 14 Pages |
Abstract
Diabetes is an important health issue because of its increasing prevalence and association with impaired wound healing. Epidermal keratinocytes with overexpressed antiangiogenic molecule thrombospondin-1 (TSP1) have been shown to impair proper wound healing. This study examined the potential involvement of keratinocyte-derived TSP1 on diabetic wound healing. Cultured human keratinocytes and diabetic rat model were used to evaluate the effect of high-glucose environment on TSP1 expression in epidermal keratinocytes, and the molecular mechanisms involved in the process were also studied. We demonstrated that high-glucose environment increased TSP1 expression in keratinocytes. In addition, increased oxidative stress induced DNA hypomethylation at the TSP1 promoter region in keratinocytes exposed to high-glucose environment. Similar findings were found in our diabetic rat model. Early antioxidant administration normalized TSP1 expression and global DNA methylation status in diabetic rat skin and improved wound healing in vivo. Because oxidative stress contributed to TSP1 DNA hypomethylation, early recognition of diabetic condition and timely administration of antioxidant are logical approaches to reduce complications associated with diabetes as alterations in epigenome may not be reversible by controlling glucose levels during the later stages of disease course.
Keywords
STZ5-AZA-2'-deoxycytidineTSP1RlucCy5tRNA5-Aza-dCMSPNADPHPVDFDABSDSPBS3,3′-diaminobenzidine tetrahydrochlorideBSAdUTPMethylated DNA immunoprecipitationMethylation-specific PCRROSbovine serum albuminstreptozotocintransfer ribonucleic acidThrombospondin-1Tris-EDTADiabetes mellitussodium dodecyl sulphateAgePolyvinylidene difluoride membraneVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)Advanced glycation end-productPhosphate-buffered salinenicotinamide adenine dinucleotide phosphatepolymerase chain reactionPCRReactive oxygen species
Related Topics
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Medicine and Dentistry (General)
Authors
Cheng-Che E. Lan, Shu-Mei Huang, Ching-Shuang Wu, Chin-Han Wu, Gwo-Shing Chen,