Study of Mice Suggests Key to Treating Scar Tissue in Liver
Daniel J. DeNoon
WebMD Medical News
Louise Chang, MDDec. 27, 2007 -- Working with mice, researchers have found a
molecule that prevents -- and even reverses -- formation of scar tissue
in damaged livers.
The finding promises new treatments for cirrhosis and other scarring diseases of the liver, and perhaps for other scarring-related conditions such as pulmonary fibrosis, scleroderma, and burns.
Livers damaged by disease, toxins, or injury tend to develop excessive scar tissue -- a
condition called liver fibrosis. This process lies at the heart of
cirrhosis, in which bands of scar tissue overgrow the liver. There's
currently no sure way to prevent or reverse this process once it's
But excessive scarring happens only when a protein
called RSK is activated in liver cells, find Martina Buck, PhD, and
colleagues at the University of San Diego and the San Diego VA
Mice genetically engineered to produce
an RSK-blocking peptide did not develop liver fibrosis when poisoned
with a liver toxin. And when the peptide was injected into normal mice,
it protected them against the liver toxin.
mice had severe liver fibrosis, while all mice that received the RSK
inhibitory peptide had minimal or no liver fibrosis," Buck says in a
Scar tissue is made up of a natural material
called collagen. Liver cells called hepatic stellate cells (HSCs) don't
make much collagen unless activated by the stress of injury or disease.
Once activated, however, these cells make way too much collagen. The
result: scar tissue.
The RSK inhibitory peptide causes these activated HSCs to self-destruct, while normal liver cells continue to heal the liver.
"Remarkably, the death of HSCs may also allow recovery from injury and reversal of liver fibrosis," Buck says.
Human HSCs work much the same way as mouse HSCs, so the findings should apply to human disease, the researchers suggest.
Buck and colleagues are hopeful that the RSK inhibitory peptide will be the model for a future human drug.
speculate that these findings may facilitate the development of small
molecules potentially useful in the prevention and treatment of liver
fibrosis," Buck and colleagues conclude. "Blocking the progression of
liver fibrosis would decrease development of primary liver cancer in these patients since the majority of [liver cancers] arise in cirrhotic livers."
Buck and colleagues report their findings in the Dec. 26 issue of the online journal PloS One.
SOURCES: Buck, M. and Chojkier, M. PloS One, Dec. 26, 2007; vol 2: pp e1372. News release, University of California San Diego.
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