2010-ASCB-Press-Book - page 5

T h e A m e r i c a n s o c i e t y f o r C e l l B i o l o g y
News from
The American Society
for Cell Biology
50th Annual Meeting
Philadelphia, PA
December 11–15, 2010
The goo that binds
10:00 am, U.S. Eastern Time
Sunday, December 12, 2010
Cornelia Tölg
Eva Turley
London Health Sciences Centre/
London Regional Cancer
800 Commissioners Rd. East
London, ON N6A 5W9
519-685-8600, ext. 53677
Author presents
Sunday, December 12, 2010
1:00 pm–2:30 pm
Session: Epithelia
Exhibit Halls A/B/C
Program: 619
Board: B1002
Use of Hyaluronan Binding
Peptides for Control of Wound
Repair–Associated Fibrosis
C. Tölg, E. Turley
London Regional Cancer
Program, London, Ontario,
R. Savani
University of Texas Southwest-
ern Medical Center, Dallas, TX
D. Bagli
Hospital for Sick Children,
Toronto, Ontario, Canada
F. Winnik
Université de Montréal,
Montreal, Quebec, Canada
M. Cowman
Polytechnic Institute of New
York University, New York, NY
A ubiquitous sugar molecule,
hyaluronan shows a new role in
repairing deep wounds without
espite its ubiquity, hyaluronan,
also known as hyaluronic acid,
didn’t get much respect until re-
cently. A long, viscous sugar, hyaluronan
is found in all manner of living things
(except plants) and until the late 1970s it
was considered little more than the “goo”
in the extracellular matrix. Since then,
hyaluronan has emerged as a biologi-
cal star in everything from embryonic
heart development to tumor metastasis
to wound repair. Now hyaluronan steps
out as the key to robust healing and less
scarring in deep wounds, according to
Canadian researchers.
A major component in skin, hyaluro-
nan was long thought to play a compli-
cated although unclear part in closing
deep wounds and minimizing fibrotic
scarring in repaired tissue. The picture
is getting clearer. Cornelia Tölg of the
London (Ontario) Regional Cancer
Program and colleagues in Canada
and the U.S. report success in manipu-
lating the wound repair process by us-
ing a small peptide to block hyaluronan
fragments from setting off a cellular
pathway linked to inflammation. Using
this peptide, they report a repair process
that resembles regeneration
typically observed during
embryogenesis. The results
have clinical implications
for human wound healing,
according to Tölg.
The researchers have
identified a small peptide
made up of 15 amino acids,
which blocks fragmented
hyaluronan molecules from
binding to a receptor on
epidermal and dermal cells,
thus dampening the trigger
for inflammation. Wounds
in rats treated with a single
dose of this fragment blocker, called pep-
tide 15-1, had significantly less scarring
and stronger regenerated tissue than did
control subjects, researchers report.
The relationship between hyaluronan
levels and tissue regeneration is paradoxi-
cal. Hyaluronan levels are extremely high
in developing embryos and newborns,
who can recover readily from surgery
without scarring. But throughout adult
life, our intact hyaluronan levels drop
while the proportion of broken hyaluro-
nan molecules rises. The problem, says
Tölg, is that whereas the intact hyaluro-
nan molecule promotes strong healing,
hyaluronan fragments engage the awk-
wardly named “receptor for hyaluronan-
mediated motility,” or RHAMM, setting
off inflammation that can result in fibrotic
scarring and weak granulated tissue.
Tölg and colleagues used micro-
scopic beads coated with hyaluronan to
fish out two small peptides that bound to
the shape of the molecule. One of them in
particular, peptide 15-1, showed an affin-
ity for fastening itself to hyaluronan frag-
ments, effectively keeping them from the
RHAMM. A single-dose treatment with
peptide 15-1 reduced wound contraction,
collagen deposits, inflammation, and
growth of unwanted new blood vessels,
Tölg reports.
The relationship between hyaluronan levels and tissue regeneration (top)
is paradoxical. The intact hyaluronan molecule promotes strong healing
and yet hyaluronan fragments engage a cellular receptor that sets off an
inflammation pathway, resulting in fibrotic scarring and weak granulated
tissue (bottom right). By blocking hyaluronan fragments (bottom left),
researchers were able to encourage regenerative repair.
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