The role of Cx43‐mediated signalling in diabetic and non-diabetic wound healing events

A problem presented at the UK MMSG Strathclyde 2010.

Presented by:
Dr Patricia Martin (Department of Biological & Biomedical Sciences, Glasgow Caledonian University)
Dr Catherine Wright (Department of Biological & Biomedical Sciences, Glasgow Caledonian University)
Participants:
M Al-husari, CG Bell, JR Caffrey, ETY Chang, UZ George, K Giorgakoudi, PE Martin, SR McDougall, FL Roberts, A Shabala, P Ward, MG Watson, D Webb, C Wright

Problem Description

A major complication for patients with type II diabetes is delayed wound healing and ulceration. This can result in chronic non‐healing wounds with leg and foot ulceration and lower extremity amputations. Following 20 weeks of standard care around 67% of diabetic foot ulcers remain unhealed. Conventional treatments are labour intensive, costly and relatively ineffective, whilst pharmacological approaches have yet to show clinical utility. Thus defining new therapeutic agents that can be directly incorporated onto a wound bed in a topical form could provide significant improvements in patient care and reduce costs.

The gap junction protein connexin43 (Cx43) exhibits differential remodelling in ‘normal’ and ‘chronic’ wounds, and small peptides targeted to this protein (CMPs) improve wound closure rates in ex vivo and in vitro organotypic skin model systems. In the experiments, we can compare cell dynamics during cell adhesion and migration under differing cellular conditions in the presence or absence of the peptides.

We propose to assess modes of cell movement and time taken for 50% closure of the ‘wound gap’ by determining spatio‐temporal differences in cellular events. An ideal outcome from the workshop would be the development of an accurate and validated description of the wound healing process – incorporating key factors, such as individual cell movement, cell‐cell interactions, cell divisions, protein production and utilization.

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Study Group Report

During the week long workshop four models were developed, all of which address slightly different aspects of the role of connexins in wound closure events. Each of the extracted parameters can now be further explored and developed to provide a platform for quantifying the observed cellular events, providing cellular information on the impact of remodelling connexin signalling and adhesion events on cell migration and motility responses. Such an integrated systematic approach has potential to refine experimental needs, reduce patient sourced material and minimise animal numbers prior to in vivo trials of the peptides on wound closure events.

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Follow-Up Activities

The following follow-up meetings have occured to continue work on aspects of this problem:

2011 Wound Healing Follow-up Meeting
Wednesday 6th to Thursday 7th April 2011, Glasgow Caledonian University

The following funding for further work has been obtained to investigate aspects of this problem:

Biomathematical modelling of Connexins in wound healing events
GCU Institute of Health, three-month PDRA, £10k, January to March 2011.
Defining the role of connexins in diabetic and non diabetic wound healing events
GCU Institute of Applied Health, PhD studentship, October 2011 to September 2014.