A new molecular trail identified in alcohol -related liver disease

Excessive alcohol consumption causes alcoholic liver disease, and about 20% of these cases develops to fatty fatitis (ASH), which can lead to cirrhosis and liver failure. Early diagnosis and treatment are therefore extremely important. The research team Kaist identified a new molecular mechanism in which alcoholic liver cells increase reactive oxygen forms (ROS), leading to cell death and inflammatory answers. In addition, they discovered that Kupffer cells, immune cells living in the liver, act as a “double function regulator”, which can either promote or suppress inflammation through interaction with liver cells.

Kaist (President of Kwang-Hyung Lee) announced the 17th place that the research team led by Professor WON-L Jeong from the Graduate School of Medical Science and Engineering, in cooperation with Professor Won Won Won Kim’s Team at the Seul National University Medical Center, discovered a molecular path of liver damage and liver damage and liver inflammation caused by alcohol consumption. This discovery contains new tips on the diagnosis and treatment of alcohol -related liver disease (ALD).

Professor Won-Il Jeong’s research team said that during chronic alcohol consumption, the expression of the VGLUT3 glutamate bubble transporter increases, which leads to the accumulation of glutamate in hepatocytes. Later symptoms of drinking causes rapid changes in intracellular calcium levels, which then releases the secretion of glutamate*. The secreted glutamate stimulates the fog of glutamate receptor on the macrophages of the liver resident (Kupffer cells), which induces ROS production and activates the pathological trail, which causes death and inflammation of hepatocytes.

A particularly groundbreaking aspect of this study is that damaged hepatocytes and Kupffer cells can create “pseudosynaps” – a structure similar to a synapse, which previously believed that it occurs only in the brain – in order to replace their signals. For the first time such a phenomenon was identified in the liver.

This pseudosynaps is created when hepatocytes are expanding (ballooning) due to alcohol, physically attached to Kupffer cells. Simply put, damaged hepatocytes not only die – they send signals of anxiety to nearby immune cells, which prompted the answer.

This discovery proposes a new paradigm: even in peripheral organs, direct structural contact between cells can enable signal transmission. It also shows that damaged hepatocytes can actively stimulate macrophages and induce regeneration through cell death, revealing the “autonomous function of recovery” of the liver.

The team also confirmed in animal models that the genetic or pharmacological braking of VGLUT3, MGLUR5 or an enzyme producing ROS Nox2 reduces alcoholic liver damage. They also confirmed that the same mechanism observed in animal models was present in people from ALD by analyzing blood and liver samples.

These discoveries can be used as new molecular goals for early diagnosis and treatment of ash in the future. “

Professor Won -il Jeong from Kaist

This study was jointly conducted by Dr. Keungmo Yang (currently in the Yeouido Hospital St. Mary’s Hospital) and Kyurae Kim, a PhD student at Kaist, who was the coexisting authors. He was conducted in cooperation with the professor won the Kim team at the Seul National University Boramae Medical Center and was published in the journal July 1.