title: High-glucose environment increased thrombospondin-1 expression in keratinocytes via DNA hypomethylation.
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.
authors.affiliation: Department of Dermatology, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Dermatology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: laneric@kmu.edu.tw.
authors.forename: Cheng-Che E
authors.initials: CC
authors.lastname: Lan
authors.affiliation: Department of Dermatology, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Dermatology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Huang
authors.affiliation: Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Ching-Shuang
authors.initials: CS
authors.lastname: Wu
authors.affiliation: Department of Dermatology, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Dermatology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chin-Han
authors.initials: CH
authors.lastname: Wu
authors.affiliation: Department of Dermatology, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Dermatology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: d700086@kmu.edu.tw.
authors.forename: Gwo-Shing
authors.initials: GS
authors.lastname: Chen
mesh_terms: D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D019175:DNA Methylation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D019700:Thrombospondin 1 / Q000378:metabolism*; D014945:Wound Healing
chemical_list: D003470:Culture Media; D019700:Thrombospondin 1; C582391:Thbs1 protein, rat; D005947:Glucose