Too Much ETP Is Bad For The Liver

Elevated levels of endotrophin, or ETP, result in liver cell death, leading to inflammation and fibrosis of the liver, scientists find.

AsianScientist (Jan. 29, 2019) – An international team of scientists has identified a biomarker for the early detection of chronic liver disease. They reported their findings in the Journal of Pathology.

Chronic liver disease is known as a silent killer as it shows no obvious symptoms until the disease has progressed to an advanced stage. Making a proper diagnosis in the early stages of liver disease is critical to slow or prevent disease progression.

In the present study, an international team of researchers led by Professor Park Jiyoung at Ulsan National Institute of Science and Technology, South Korea, has identified a mechanism by which the protein scaffold, or extracellular matrix, surrounding liver cells plays a role in chronic liver disease. Their findings may serve as a new diagnostic marker and therapeutic target for the condition.

The researchers revealed that an extracellular molecule called endotrophin (ETP) contributes to liver pathology. Previously, ETP was known to be elevated in obesity or diabetes and is associated with fibrosis, inflammation and metabolic dysfunction in fat tissues, as well as systemic insulin resistance.

When the researchers examined the liver tissues from hepatocellular carcinoma (HCC) patients, they noted the presence of ETP in tumor-neighboring regions, which was strongly associated with poor prognosis. They then directly assessed the function of ETP in liver tissues in a mouse model where they could specifically induce the overproduction of ETP in the livers of mice. They found that ETP overexpression triggered liver cancer in the mice.

Delving deeper into the mechanism by which ETP overexpression leads to liver dysfunction, the researchers discovered that ETP mediates interactions between hepatocytes and other cell types in the liver. The signaling pathways triggered by ETP kill hepatocytes, and substances released from the dead hepatocytes cause inflammation. Over time, the continuous cycle of cell death, inflammation and fibrosis results in liver dysfunction and even liver cancer.

“Therapeutic antibodies that inhibit the activity of ETP can be used to break the vicious circle that occurs between liver tissue cells,” said Park. “This suggests that ETP may be developed as a target substance for a specific therapeutic agent for treating patients with chronic liver disease.”

Park also emphasized that ETP is an extracellular substance that appears in the early stage of chronic liver disease and an be easily detected in blood. Hence, ETP may also serve as an early diagnostic marker for liver ailments.

The article can be found at: Lee et al. (2018) COL6A3-derived Endotrophin Links Reciprocal Interactions Among Hepatic Cells in the Pathology of Chronic Liver Disease.


Source: Ulsan National Institute of Science and Technology; Photo: Shutterstock.
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