Exploring human skin explant models for inflammation and impaired wound healing.

Arekion, Kelly Rebekah (2022) Exploring human skin explant models for inflammation and impaired wound healing. Masters thesis, University of East Anglia.

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Diabetic foot ulcers (DFUs) are a leading cause of non-traumatic limb amputations and can have a severe negative impact on the quality of life of diabetic patients. The main cause of DFUs is inefficient wound healing which is a result of a combination of a number of characteristic symptoms of diabetes mellitus, including chronic inflammation, hyperglycaemia and decreased immune function. This project utilises a human skin ex vivo model to investigate the genes which may be differentially expressed in diabetic patients compared to healthy patients and their subsequent effects on wound healing of the skin. This could help to obtain a further understanding of the deregulation of the wound healing cascade that can occur as a result of the various abnormalities in homeostasis of the body in a diabetic patient. Through subjecting human skin explants to various stimulants that mimic diabetic conditions (chronic inflammation, hyperglycaemia and bacterial infection) microarray analysis, immunohistochemistry and qRT-PCR methods were used to investigate differential gene/protein expression in the stimulated skin compared to unstimulated controls. Various genes were found to be up/downregulated in this model. In particular, the genes indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO2) – which were selected as the main focus of this study, were found to be upregulated. The protein products of these genes; TDO2 and IDO1 are enzymes that are essential for the metabolism of the essential amino acid tryptophan through the kynurenine pathway. Through further analysis via literature mining, a potential correlation between these genes and wound healing was found. This was then tested using the TDO2 inhibitor 680C91 in a scratch wound healing assay using 3T3 mouse cells, which suggested that inhibition of TDO2 substantially decreases the rate of wound healing with an additional effect of altering glucose concentrations. These data suggest a possible correlation between TDO2 and diabetic wound healing.

Item Type: Thesis (Masters)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Chris White
Date Deposited: 27 Mar 2023 10:09
Last Modified: 27 Mar 2023 10:09
URI: https://ueaeprints.uea.ac.uk/id/eprint/91686

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