Essay Prize: The molecular basis for pathological scarring By Guy Stanley, Nottingham University

guy.stanley@gmail.com

http://linkedin.com/in/drguystanley

Introduction

As the winning entry in Restore’s Essay Prize Competition for medical students,

this poster summarises our current understanding of the key molecules, which

influence pathological scarring.

A search of the PubMed database revealed a pattern to research: There are

three principle variables in the context of three areas of research. A major play-

er in the literature is TGF-β, a family of molecules with a central role in scar-

ring.

Conclusion

Current research simplistically classifies molecules as pro– or anti-scarring.

In reality the picture is less black and white. Nature has built in multiple

mechanisms, making it difficult to isolate the sole function of a single

agent. The overall mechanism for scarring remains unclear and future work

looking at in vivo models will help refine our understanding of this subject.

Physiological wound healing

A scar is a remnant of the inflamma-

tory, proliferative & remodelling

phases of wound healing.

The ECM (extracellular matrix) is

the structural home for cells and key

molecules of scarring. Collagen is a

major protein in the ECM, which en-

dows strength to scars. It is overex-

pressed in pathological scars.

Fibroblast type cells are central to

the creation of scars as they create

collagen and maintain the ECM.

Acknowledgements

With the generous support of Restore and the assistance of ReSURGE Af-

rica, I will be undertaking a 5 week Summer project at the Burns & Plastics

Unit, Korle Bu Teaching Hospital, Accra, Ghana.

Extracellular Membrane (ECM) constituents

Hyaluronic acid has a long association with scarring and its presence may

be associated with reduced scarring.

Elastin is less well researched but

may promote reduced scarring.

Some distinct proteoglycans and gly-

coproteins are seen in over active

scars but evidence is lacking.

Clinical factors

Corticosteroids, in pathology , degrade

collagen in scars. In treatment, they reduce

pathological scars.

Oestrogen decreases after the menopause

and there is some evidence relating it to

scar quality.

Androgens, surging at puberty, indirectly

promote Acne. 1% of 18-70 year olds

have acne scars.

Lifestyle & disease play a broad role. Smoking renders scars less vascular

while lack of Vitamin C reduces collagen’s strength. Without some trace

metals like Zinc, needed in wound metabolism, scars are weakened.

Physiological

scarring

TGF-β

Signalling molecules

ECM constituents

Signalling molecules

Transforming Growth Factor-Beta (TGF-β), in its

numerous forms, is the most studied molecule. In-

flammatory cytokines, Transcription factors and

signalling pathways, associated with TGF-β have

been investigated. TGF-β is thought to be ‘the

scarring molecule’ but has not proved to be an ef-

fective treatment during clinical trials.

Many inflammatory cytokines (notably Interleu-

kins), gene transcription factors and signalling

pathways (WnT/β-catenin) are being investigated

for their anti-scarring properties. None have been

shown effective in clinical trials so far.

Figure 1: The pattern of scarring research

Figure 3: A graphical

representation of TGF-β

receptor molecule.

Figure 2: An immunofluorescence

image of fibroblast cells in the ECM

Figure 4: A molecule of Hyaluronic

Acid.

Figure 5: Hypertrophic scars on

a patient’s forearm.