COMPARATIVE GLYCOMICS OF DIABETIC AND NON- DIABETIC SKIN REVEAL SIGNIFICANT DIFFERENCESDURING WOUND HEALING
Veronica R. Haywood1, Sylvain D. Lehoux2, Emily E. Rouse2, Karen Colley1, Luisa A. DiPietro1.
1UIC, CHICAGO, IL, USA, 2Beth Israel Deaconess, Boston, MA, USA.
In 2017, Diabetes Mellitus (DM) and its comorbidities placed a 327 billion-dollar burden on the US economy. Approximately 33% of this burden can be attributed to diabetic lower extremity ulcers (DLEU’s/DFU’s). As the economic cost of DM continues to rise, it is imperative that biomarkers are identified to predict ulcer development and healing. Previous studies in our lab identified several glycosylation-related genes that are differentially regulated between diabetic and non-diabetic skin and wounds. To determine whether DM impacts downstream changes in skin and wound glycosylation, we compared the N- and O-linked glycan profiles of C57BL (WT) and db/dbLepr (DM) mouse skin and excisional wounds using MALDI-TOF mass spectrometry. Skin samples were collected at baseline and days 1, 3, and 10 post wounding to reflect the early inflammatory, mid- inflammatory, and proliferative phases of wound healing. Glycan profiling identified a total of 175 N-linked and 25 O-linked glycans in WT and DM skin and wounds. Among the glycans observed, only 25.7% of the N-linked glycans have been identified in mouse serum. When examined individually, 11 N-linked and 10 O-linked glycans were differentially regulated between WT and DM mice during wound healing (p<0.05). When examined by structural features, diabetic wounds demonstrated a 2 to 4-fold increase in highly fucosylated, complex N-glycans (p<0.05) during the inflammatory phase of wound healing. Additionally, diabetic wounds displayed increased core 2 fucosylation and blunted sialylation of core 1 and core 2 O-linked glycans (p<0.05) between the inflammatory and proliferative phases of wound healing. Overall, this data suggests that there may be a metabolic preference for fucosylation over sialylation of N- and O-linked glycans during the inflammatory phase of wound healing in diabetic mice. This change may contribute to the altered immune response observed in DM.
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