Liver Fibrosis “Off Switch” Discovered in Mice

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Chronic alcohol abuse and hepatitis can injure the liver, leading to a buildup of collagen and scar tissue, which is called liver fibrosis. For a patient with liver disease, the liver fibrosis process is often key to treatments. So what if we can find a way to just “switch off” the process?



Researchers at University of California San Diego School of Medicine recently demonstrated that liver fibrosis may be controlled by manipulating a special population of liver cells called hepatic stellate cells (HSCs).



3 forms of HSCs


There are 3 forms of HSCs in the liver: naïve in healthy people, activated in people with liver disease, and inactivated in people who have recovered from liver fibrosis. Researchers found that by manipulating the specific transcription factors, they can turn the cells “on” or “off.”


"We are excited to discover that HSCs have this flexibility, and that we can change their type by manipulating the molecules involved," said Tatiana Kisseleva, MD, Ph.D., associate professor of surgery at UC San Diego School of Medicine. "These insights may allow us to develop new ways to stop the progression of liver fibrosis."




Find the “key”


The researchers decided to understand the mechanism that switches HSCs from their naïve to active stats, and find ways to stop the process and inactivate collagen-producing HSCs, which can indicate the beginning of liver fibrosis.


"We essentially found that we can help PPARγ put a stop to collagen production by activated HSCs," Kisseleva said.



For now, weight loss is the only known way to decrease liver fibrosis related to non-alcoholic steatohepatitis (NASH) and nonalcoholic flatty liver disease (NAFLD). Therapeutic drugs to slow the progression of disease are only available in advanced stages, where NASH has led to liver cirrhosis. Early liver transplantation is the only proven cure, but is offered very limitedly.


The team are working to explore the role of other transcription factors involved in the process, and searching for activators and inhibitors. Hope a new drug can be produced to help people with liver diseases.


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