KAIST Unveils Mechanism of Hepatitis Induced by Alcohol for the First Time

[Financial News] KAIST researchers have identified a new molecular mechanism by which reactive oxygen species (ROS) generated during alcohol consumption lead to hepatocyte death and inflammatory responses. They also revealed for the first time in the world that hepatocytes form synapse-like structures and induce inflammation through a 'new neurological pathway' similar to synapses in the nervous system.
KAIST (Korea Advanced Institute of Science and Technology) announced on the 17th that the research team led by Professor Jung Won-il of the Graduate School of Medical Science, in collaboration with Professor Kim Won's team at Seoul National University Boramae Hospital, has elucidated the molecular mechanism of liver damage and inflammation (Alcohol-associated Steatohepatitis, ASH) caused by alcohol consumption, providing clues for the diagnosis and treatment of alcoholic liver disease.
Professor Jung Won-il's research team confirmed that during chronic alcohol consumption, the increased expression of 'vesicular glutamate transporter (VGLUT3)' leads to the accumulation of glutamate in hepatocytes, and subsequent binge drinking induces changes in intracellular calcium levels, promoting glutamate secretion.
Glutamate, a type of amino acid, is involved in cell signaling, protein synthesis, and energy metabolism in various tissues, including the brain and liver, and excessive amounts can cause neuronal overexcitation, leading to cell damage or death.
The secreted glutamate stimulates the glutamate receptor (mGluR5) of Kupffer cells, resident macrophages in the liver, inducing the generation of reactive oxygen species (ROS), which forms a pathological pathway leading to hepatocyte death and inflammatory responses.
The core of this study is that for the first time, it was identified that hepatocytes and Kupffer cells form a 'pseudosynapse', a structure similar to synapses observed only in the nervous system, to exchange signals during alcohol consumption.
In fact, the research team demonstrated through animal models that genetic or pharmacological inhibition of glutamate transporter (VGLUT3), glutamate receptor (mGluR5), and reactive oxygen species-generating enzyme (NOX2) reduces alcohol-mediated liver damage. Based on this mechanism, the team analyzed the blood and liver tissues of patients with alcoholic liver disease, suggesting that this mechanism can be clinically applied.
Professor Jung Won-il of KAIST Graduate School of Medical Science said, “This can be used as a new molecular target for diagnosis or treatment in the early stages of the onset of Alcohol-associated Steatohepatitis (ASH).”
This research was conducted in collaboration with Professor Kim Won's team at Seoul National University Boramae Hospital and was published in the international journal 'Nature Communications' on July 1st.
 


jiany@fnnews.com Youn Ji-an Reporter