Abstract
Wound repair is vital for restoring skin integrity and function following damage.It is a complex process that requires the coordination of multiple cell types.
One of the key stages of wound repair is inflammation, which is essential for
the clearance of debris and pathogens at the wound site and can even
coordinate downstream repair events. However, when inflammation becomes
dysregulated, or fails to resolve it can lead to a multitude of pathologies
associated with wound healing including hyperpigmentation and chronic
wounds. The precise molecular mechanisms driving these pathologies remain
unclear, resulting in a lack of truly effective treatment options for patients. Here,
I have used the zebrafish (Danio rerio) as a model system to explore the roles
of two lesser studied cell types in the context of wound repair: melanocytes
which drive wound hyperpigmentation, and adipocytes which are often
dysregulated in obese and diabetic patients who suffer from chronic wounds.
Taking advantage of the optical transparency of zebrafish, I investigate the
dynamic interaction between inflammatory cells and both melanocytes and
adipocytes. I show here that macrophages drive the recruitment of
melanocytes to a wound causing wound hyperpigmentation, in part, through
signalling via ACVR2A, as revealed by a proteomic comparison study. I also
show through light and electron microscopy that macrophages crown wound
edge adipocytes, and that these adipocytes subsequently lose their lipid and
cellular identity. My data demonstrate the importance of the impact of
inflammation upon other cell lineages at the repair site, and how the models
presented here could reveal potential targets for therapeutic interventions to
improve the outcome of pathologic cases of wound repair.
| Date of Award | 5 Dec 2023 |
|---|---|
| Original language | English |
| Awarding Institution |
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| Supervisor | Paul B Martin (Supervisor) & Anne J Ridley (Supervisor) |