This molecule could be behind liver fibrosis



The liver is a crucial organ in the body's processing of all the many substances we put into it, including food, drink, alcohol, and narcotics. When the liver malfunctions, the results might be fatal. Scarring, also known as liver fibrosis, is the primary cause of many liver illnesses, including hepatitis and Non-Alcoholic SteatoHepatitis, or NASH. At this time, there are no medications available to cure this scarring.

In order to find possible targets for medications in the future, researchers are looking into the underlying causes of liver fibrosis. A chemical responsible for the bile duct cells' unchecked proliferation inside the liver has been identified by a U-M study.

The bile duct cells are injured in diseased livers, according to Liangyou Rui, Ph.D., the Louis G. D'Alecy Collegiate Professor of Physiology. The liver must constantly produce new bile duct cells, but occasionally these cells malfunction, resulting in inflammation and scarring.

Rui notes that this increased bile duct formation is known as a ductular response. Patients with ductular reaction get worse outcomes and greater illness complications.

They describe a chemical called NIK, which is highly activated in the dysfunctional bile duct cells, in their work, which was published in the journal Nature Communications. The NIK gene was eliminated from the bile duct cells using a genetically altered mouse model.

Rui remarked, "When eliminated, you stop all of those awful things from happening. Furthermore, the liver disease of normal mice was alleviated by administering NIK inhibitors, chemicals that can impede the activity of NIK.

How does NIK lead to illness? In response to the many toxins that the liver is exposed to while performing its usual functions, NIK promotes the regeneration of bile duct cells under normal circumstances. However, some infections, medications, or other adversities can subvert this natural reparative process, causing excessive growth, the ductular reaction, as well as the release of inflammatory mediators that cause scarring.

To stop this scarring process, the team plans to collaborate with researchers at U-M and other institutions to create novel NIK-inhibitors. The findings may also be applied as a therapy for cholangiocarcinoma, a specific type of liver cancer that makes up one-third of all liver cancers but has few available therapeutic choices.

Zhiguo Zhang, Xiao Zhong, and Hong Shen from the U-M Medical School Department of Molecular & Integrative Physiology are the paper's initial authors. The senior corresponding author is Dr. Rui. Liang Sheng, Suthat Liangpunsakul, Anna S. Lok, M Bishr Omary, and Shaomeng Wang are additional contributors.

Michigan Medicine - University of Michigan

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