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