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2009/12/17

CIC bioGUNE research scientists identify risk gene affecting liver regeneration

Researchers from the CIC bioGUNE and the Centre for Biomedical Network Research into Hepatic and Digestive Diseases, CIBERehd, have discovered that deficiency of a certain gene (GNMT) affects liver regeneration and proliferation, and produces greater susceptibility when the liver is damaged. These findings have been published recently in the journal Hepatology.

The researchers have shown that deficiency of the GNMT gene increases susceptibility of the liver to damage caused by toxic agents such as alcohol or certain medicines. They have found GNMT deficiencies in patients with steatosis (accumulation of fat in the liver), fibrosis (a step prior to cirrhosis) and hepatocellular carcinoma (cancer of the liver).

This research has been carried out jointly with the Keck School of Medicine (U.S.A.) and Vanderbilt University (U.S.A.), and together with these scientists the group at the CIC bioGUNE have used genetic engineering to develop a mouse model that lacks GNMT. They have therefore been able to show that GMNT is the main gene behind liver metabolism of the SAMe molecule (S-Adenosylmethionine), which is important in turn for ensuring that liver cells multiply correctly.

Previous studies by this team had shown that excessively high levels of SAMe alter the way that hepatocytes function, with two direct consequences; firstly, that they cause an uncontrolled proliferation of the liver which leads to the development of a hepatocellular carcinoma, and secondly, that this anomalous proliferation prevents any regeneration of the deteriorated liver and makes it more susceptible to hepatic damage.

It has now been confirmed that a complete lack of the GNMT gene means uncontrolled SAMe levels, and that this means that the liver is unable to stop hepatic cells from proliferating anomalously and out of control, giving rise to the appearance of a tumour.