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Glycosylation and Sialylation During Wound Healing
thesisposted on 01.08.2019 by Veronica A Haywood
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Chronic wounds significantly increase morbidity and mortality and are a consequence of disease including diabetes. Previous studies have demonstrated that glycosylation, a post- translational protein modification whereby carbohydrates are added to proteins, is altered during corneal wound healing and in diabetes. However, no studies have examined whether differential glycosylation occurs during wound healing between different tissue types, in diabetic skin wound healing, and/ or among tissues with different healing potentials. Since the skin exhibits impaired healing when compared to the oral mucosa and diabetic skin is impaired in relation to non-diabetic skin, we hypothesize that glycosylation related gene expression is altered among tissues with differential healing potentials. This study examines the differential regulation of glycosylation related genes and protein sialylation between uninjured tissue and wounds of the skin and oral mucosa using microarray analysis of glycosylation related genes and lectin blot analysis of protein sialic acid carbohydrates. Additionally, differential regulation of glycosylation related genes and glycans from diabetic and non- diabetic skin and wounds were examined via high throughput qualitative polymerase chain reactions and semiquantitative glycomics analysis. Overall, this study demonstrates that 3 glycosylation related genes related to mucins and glycogenolysis respectively are downregulated, while 18 genes associated with neutrophil degranulation, sulfation, and polysialylation among others are upregulated in tissues with impaired healing. Furthermore, time dependent increases in protein sialic acids and polysialic acids and were observed in the skin when compared to the oral mucosa while diabetic skin exhibited increases in N-linked glycan sialic acids and fucosylated, sialosyl-poly-N- acetyllactosamines when compared to non- diabetic skin. Interestingly, increased sialic acid carbohydrates have been observed in other models of acute inflammation and both polysialic acid and fucosylated, sialosyl-poly-N- acetyllactosamine carbohydrate determinant are involved in selectin- selectin ligand mediated inflammatory responses. In conclusion, protein glycosylation is differentially regulated in a tissue and disease specific manner that is associated with the inflammatory response during wound healing. Furthermore, this altered glycosylation likely contributes to the decreased healing potential observed in the skin when compared to the oral mucosa and in diabetic skin when compared to non- diabetic skin respectively, however, further validation is required.