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Advanced glycation end products disrupt cutaneous wound healing through inhibiting nitric oxide signalling

Summary of project

In the UK an estimated 200,000 people suffer from chronic wounds. These severely impact on patient quality of life and long-term health. Many of these cases are underpinned by diabetes, which strongly delays normal wound healing responses. The cost to the NHS of caring for patients with a chronic wound is conservatively estimated at £2.3bn–£3.1bn per year. This figure is set to rise sharply as diabetes levels continue to grow. Healing in acute wounds follows a progression through a series of steps including coagulation, inflammation, skin cell (fibroblast and keratinocyte) recruitment, proliferation, and connective tissue production and remodelling. Chronic wounds result from heightened inflammation and a disruption in these processes.

A wealth of experimental and clinical wound healing studies have established nitric oxide (NO) as a critical mediator of normal tissue repair. NO is produced by a range of cells within the wound bed, where it promotes keratinocyte and fibroblast migration and proliferation as well as connective tissue production, all key steps in successful healing. The wound healing promoting effects of NO are reduced in diabetic patients, but the underlying mechanisms remain to be discovered.

Hyperglycaemia, observed in diabetes, promotes the formation of pathogenic Advanced Glycation End products (AGEs). AGEs have been shown to delay wound healing responses in fibroblasts and keratinocytes. Our preliminary data suggests that AGEs block NO signalling, which may help explain the heightened incidence of chronic wounds observed in diabetic individuals. In this project you will test the hypothesis that Advanced Glycation End products (AGEs) limit the ability of nitric oxide (NO) to induce human skin fibroblast and keratinocyte wound healing responses. Once you have characterised these functional responses you will identify the underpinning molecular mechanisms. Identifying how diabetes induces chronic wound development will be key to designing new therapeutics to restart normal cutaneous healing.


Entry requirements

2:1 BSc (Hons) and/or merit at MSc level in Biomedical Science or related area.


Supervisors

Title and name:
Dr Wayne Roberts
Position:
Lecturer in Medical Sciences
Email address:
Telephone number :
Work+44 (0) 1274 232131
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Title and name:
Dr Kirsten Riches
Position:
Lecturer in Biochemistry
Email address:
Telephone number :
Work+44 (0) 1274 232145
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