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α‐ketoglutarate is associated with delayed wound healing in diabetes
Author(s) -
Tan Qin,
Wang Wei,
Yang Chuan,
Zhang Jinglu,
Sun Kan,
Luo Heng cong,
Mai Li fang,
Lao Yu,
Yan Li,
Ren Meng
Publication year - 2016
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.13047
Subject(s) - wound healing , diabetic foot , medicine , diabetes mellitus , postprandial , endocrinology , matrix metalloproteinase , urine , gastroenterology , surgery
Summary Aim 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 ( TET 2) 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 TET 2 during diabetic wound healing. Methods 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 TET 2 and MMP ‐9 expression. Clinical parameters were collected, and transcutaneous oxygen pressure (Tc PO 2) levels of feet were detected. Results The levels of α‐ KG , TET 2 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 Tc PO 2 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). Conclusions The levels of α‐ KG , TET 2 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.