title: AGE-induced keratinocyte MMP-9 expression is linked to TET2-mediated CpG demethylation.
abstract: Studies have documented that unusually high expression of matrix metalloproteinase-9 (MMP-9) suppresses wound healing during the late stages of diabetic foot ulcers. Recently, it has been reported that the presence of advanced glycation end products-bovine serum albumin (AGE-BSA) resulted in a higher expression of MMP-9 in skin primary keratinocytes. The aim of the present study was to elucidate the molecular machinery that is responsible for the inappropriately high AGE-BSA-induced expression of MMP-9. It has been demonstrated that site-specific DNA demethylation played an important role in MMP-9 expression in AGE-BSA-stimulated keratinocytes. Ten-eleven translocation-2 (TET2) was up-regulated, whereas the percentage of methylation in the MMP-9 promoter was reduced. Furthermore, TET2 directly bound to a fragment surrounding the transcriptional start site in the MMP-9 promoter region, contributing to the regulation of MMP-9 expression. In addition, evidence indicated that TET2 affected the migration and proliferation in vitro of cultured skin primary keratinocytes. These findings indicated that TET2 directly interacted with the promoter region of MMP-9 in diabetic tissues and may be a novel master regulator of wound healing.
authors.affiliation: Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, GuangZhou, People's Republic of China.
authors.forename: Jinglu
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, GuangZhou, People's Republic of China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, GuangZhou, People's Republic of China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, GuangZhou, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, GuangZhou, People's Republic of China.
authors.forename: Guojuan
authors.initials: G
authors.lastname: Lao
authors.affiliation: Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, GuangZhou, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, GuangZhou, People's Republic of China.
authors.forename: Kan
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, GuangZhou, People's Republic of China.
authors.forename: Hengcong
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, GuangZhou, People's Republic of China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, GuangZhou, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Ren
authors.affiliation: Department of Endocrinology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, GuangZhou, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000073398:Demethylation / Q000187:drug effects*; D017719:Diabetic Foot / Q000188:drug therapy* / Q000473:pathology; D049308:Dioxygenases; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D004268:DNA-Binding Proteins; D017127:Glycation End Products, Advanced; D011518:Proto-Oncogene Proteins; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D049308:Dioxygenases; C541081:TET2 protein, human; D020780:Matrix Metalloproteinase 9