Thursday, June 10, 2010
Researchers from the University of Illinois at Chicago have
discovered that an unexpected cellular response plays an important
role in breaking down and inhibiting the formation of excess scar
tissue in wound healing.
Their study was published online this week in Nature Cell
Biology.
When an organism suffers severe injury, specialized cells are
"recruited" to the wound site that rapidly produce extracellular
matrix proteins such as collagen to provide structural support to
the tissue, according to Lester Lau, professor of biochemistry and
molecular biology at the UIC College of Medicine and principal
investigator in the study.
Joon-Il Jun, a postdoctoral fellow working in Lau's lab and first
author of the paper, found that fibroblasts recruited to the site
of skin wounds were entering a state of reproductive dormancy, or
cell-cycle arrest, called senescence.
This was quite unexpected, Jun said. Until now senescence was
believed to occur in cells that suffered DNA damage -- to prevent
them from proliferating and, possibly, becoming cancerous.
He discovered that the senescent fibroblasts were making proteins
that degraded the extracellular matrix and accelerated the
breakdown of collagen. The senescent cells also stopped making
collagen.
"The accumulation of senescent cells in the wound has the
biological effect of inhibiting the formation of excess scar
tissue," Jun said.
Jun also discovered that a protein called CCN1 is responsible for
turning on the senescent state in fibroblasts. He was able to show
that in mice with a mutated, non-functional form of CCN1, the
fibroblasts at the site of a skin wound did not become senescent,
and the wound developed excessive scar tissue.
Further, Jun was able to "rescue" the mutated mice by applying CCN1
protein topically to the skin wound, triggering fibroblast
senescence and limiting the formation of scar tissue.
The discovery that senescence is a normal wound-healing response in
the skin; that senescence in the wound serves an anti-fibrotic
function; and that CCN1 is the critical protein that controls this
process may prove important in understanding a wide range of
pathological conditions related to tissue scarring, said Lau.
"For example, chronic injury to the liver from a number of causes,
including viral infections, alcoholism, diabetes and obesity, leads
to fibrosis and may progress to cirrhosis," Lau said. "After a
heart attack, accumulation of scar tissue in the heart impairs its
ability to pump efficiently."
The ability to control the formation of scar tissue, or fibrosis,
has important implications for future therapies for treating
wound-healing disorders, including organ damage where functional
tissue is replaced with scar tissue, Lau said.
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Thanks to University of Illinois at Chicago for this
article.