New Clues for Liver Cirrhosis Treatment
Study of Mice Suggests Key to Treating Scar Tissue in Liver
Dec. 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 begun.
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 Healthcare System.
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.
"All control mice had severe liver fibrosis, while all mice that received the RSK inhibitory peptide had minimal or no liver fibrosis," Buck says in a news release.
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.
"We 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.