title: α-ketoglutarate is associated with delayed wound healing in diabetes.
abstract: A high level of matrix metalloproteinase 9 (MMP-9) is a predictor of poor wound healing in diabetic foot ulcers. In skin keratinocytes, site-specific DNA demethylation plays an important role in MMP-9 expression. Ten-eleven translocation enzyme 2 (TET2) protein, one member of TET family, could rely on α-ketoglutarate (α-KG) as cosubstrate to exhibit catalytic activity of DNA demethylation. Here, we aimed to explore the changes of α-KG and its relationship with MMP-9 and TET2 during diabetic wound healing.
  
  
  
  Seventy-one cases of patients with diabetic foot ulcers and 53 cases of nondiabetic ulcers were enrolled. Serum, urine and wound fluids were collected for measurement of α-KG levels and MMP-9 expression. Skin tissues were collected for the measurement of TET2 and MMP-9 expression. Clinical parameters were collected, and transcutaneous oxygen pressure (TcPO2) levels of feet were detected.
  
  
  
  The levels of α-KG, TET2 and MMP-9 were significantly increased in diabetic wound compared with nondiabetic wound (P = 0·010, 0·016 and 0·025). There was a significant correlation between a low TcPO2 and a high α-KG level of wound fluids (r = -0·395, P = 0·002). Further analysis showed that α-KG concentration had a positive correlation with both haemoglobin A1c (HbA1C) and 2 h postprandial blood glucose (PBG) (r = 0·393, P = 0·005; r = 0·320, P = 0·025, respectively).
  
  
  
  The levels of α-KG, TET2 and MMP-9 were significantly increased in diabetic wound compared with nondiabetic wound. Elevated α-KG was related to local hypoxia ischaemia status and systematic poor glycaemic control.
authors.affiliation: Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, 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, 510120, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, 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, 510120, 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, 510120, 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, 510120, China.
authors.forename: Heng Cong
authors.initials: HC
authors.lastname: Luo
authors.affiliation: Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
authors.forename: Li Fang
authors.initials: LF
authors.lastname: Mai
authors.affiliation: Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lao
authors.affiliation: Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Ren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001785:Blood Gas Monitoring, Transcutaneous; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000032:analysis; D017719:Diabetic Foot / Q000503:physiopathology*; D049308:Dioxygenases; D006801:Humans; D000860:Hypoxia; D007656:Ketoglutaric Acids / Q000032:analysis*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000032:analysis; D012867:Skin / Q000473:pathology; D014456:Ulcer / Q000503:physiopathology; D014945:Wound Healing
chemical_list: D004268:DNA-Binding Proteins; D007656:Ketoglutaric Acids; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human; D020780:Matrix Metalloproteinase 9