Washington, Dec 27: A study on mice has shown that fibrosis in the liver can not only be stopped but also reverse some of the cell damage that has already occurred, paving way for the development of a modified protein leading to the first cure for such liver diseases.
Researchers at the University of California, San Diego, say that their findings may help treat and cure conditions leading to excessive tissue scarring such as viral hepatitis, fatty liver disease, cirrhosis, pulmonary fibrosis, scleroderma and burns.
Earlier, the UC San Diego School of Medicine research team had discovered the cause of the excess fibrous tissue growth causing liver fibrosis and cirrhosis, and also developed a procedure blocking excess scar tissue in mice.
They wanted to develop in future, a therapy that would prevent or stop damage in patients suffering from the excessive scarring related to liver or lung disease or severe burns.
In the current study, Martina Buck, Ph.D., assistant professor of medicine at UCSD and the Veterans Affairs San Diego Healthcare System, and Mario Chojkier, M.D., UCSD professor of medicine and liver specialist at the VA, demonstrated that if they blocked a protein linked to overproduction of scar tissue, not only can they stop the progression of fibrosis in mice, but also reverse the earlier damage.
Liver injury like cirrhosis, caused by alcohol, initiates response from hepatic stellate cell (HSC) that gets activated by oxidative stress resulting in large amounts of collagen. Collagen is necessary to heal wounds, but too much collagen leads to scars in tissues.
It was shown in the study that HSC gets activated due to the activation of a protein called RSK, that is critical for the development of liver fibrosis.
The scientists developed an RSK inhibitory peptide to block activation of RSK after establishing that the RSK pathway would be a potential therapeutic target.
They used mice with severe liver fibrosis (similar to the condition in humans with cirrhosis of the liver) induced by chronic treatment with a liver toxin known to cause liver damage.
Mice which continued on the liver toxin were given the RSK-inhibitory peptide which blocked RSK activation and in turn stopped the HSC from proliferating. The peptide also directly activated the caspase or “executioner" protein, killing the cells producing liver cirrhosis but not the normal cells.
“All control mice had severe liver fibrosis, while all mice that received the RSK-inhibitory peptide had minimal or no liver fibrosis,” said Buck.
He explained that the excessive collagen response is blocked by the RSK-inhibitory peptide, but did not have negative effects on the liver.
“The cells continue to do their normal, healing work but their excess proliferation is controlled. Remarkably, the death of HSC may also allow recovery from liver injury and reversal of liver fibrosis,” he said.
A similar activation of RSK in activated HSC was discovered in humans with severe liver fibrosis but not in control livers, indicating the importance of this pathway in human liver fibrosis. Liver biopsies from patients with liver fibrosis also showed activated RSK.
The study is an extension of the work in 2001 in the journal Molecular Cell announcing that a team led by Buck had found that a small piece of an important regulatory protein called C/EBP beta was responsible for fibrous tissue growth, or excessive scar tissue following injury or illness.
“Six years ago, we showed a way to prevent or stop the excessive scarring in animal models. Our latest finding proves that we can actually reverse the damage,” said Buck.
Almost 800,000 people die from liver cirrhosis each year, and there is currently no treatment for it.
Excessive tissue repair in chronic liver disease induced by viral, toxic, immunologic and metabolic disorders all result in excessive scar tissue, and could benefit from therapy developed from the UCSD researchers’ findings.
The study is published in PLoS Online. (ANI)
- Americans will do anything to save life
- Rare tiny neutrinos may help scientists find out about the origins of universe
- Warning to doctors to keep using redback anti-venom
- Eating Nuts Regularly Decreases Chances of Cancer or Heart Disease: Study
- Researchers trying to make Use of Nanoparticles Properties in Glass