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 co-substrate 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.
71 cases of patients with diabetic foot ulcers and 53 cases of non-diabetic 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 measurement of TET2 and MMP9 expression. Clinical parameters were collected and transcutaneous oxygen pressure (TcPO2) levels of feet were detected.
The levels of α-KG, TET2 and MMP9 were significantly increased in diabetic wound compared with non-diabetic 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 Hemoglobin A1c (HbA1C) and 2h-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 non-diabetic wound. Elevated α-KG was related to local hypoxia ischemia status and systematic poor glycemic control. This article is protected by copyright. All rights reserved.
Clin Endocrinol (Oxf). 2016 Feb 27. doi: 10.1111/cen.13047. [Epub ahead of print]