Fibrosis Protector
A new target for the development of liver fibrosis therapy has been discovered
Scientists from Russia and Italy have studied a new cellular mechanism that prevents the development of liver fibrosis. The role of GILZ protein in the development of the disease has been studied in mice and confirmed in clinical samples. The results of the work are published in the journal Cell Death & Disease (Flamini et al., Glucocorticoid-induced leucine zipper regulates liver fibrosis by suppressing CCL2-mediated leukocyte recruitment) and can be used in the development of therapy for liver fibrosis in humans.
With fibrosis, there is an overgrowth of connective tissue and a decrease in the functional activity of the liver. The cause of fibrosis can be a viral infection, alcohol intoxication, autoimmune inflammation and other liver diseases. If left untreated, fibrosis often leads to cirrhosis of the liver and death. Inflammatory processes play an important role in the development of fibrosis – complex cascades of interaction between cells of the immune system, regulated at the molecular level. Therefore, for the treatment of fibrosis, it is necessary to understand the molecular processes underlying their occurrence and development. The most common anti–inflammatory agents – glucocorticoids - are actively used in medicine, for example, in the treatment of autoimmune diseases. However, in the case of liver fibrosis, glucocorticoid therapy leads to serious side effects.
In their study, scientists from Skoltech, the University of Perugia (Italy) and the University of Florence (Italy) studied the GILZ protein, the expression of which leads to changes in cellular processes similar to the use of glucocorticoids. First, scientists conducted experiments on a mouse model of liver fibrosis (on mice with artificially induced liver fibrosis). In such a mouse, the gene encoding GILZ was turned off and fibrosis was observed to develop more actively. The assumption about the effect of GILZ on the development of fibrosis was tested on the gene expression data of patients with liver fibrosis and confirmed that in such people the production of GILZ protein is reduced.
New data suggest that GILZ is a promising target for drugs that can help with liver fibrosis.
"It is important that the data we obtained in mice correlate with clinical data for humans. Very often, the results obtained on model objects, even mammals, are not then confirmed in clinical practice. Now we can expect that the effect on the signaling pathway in which the GILZ protein is involved can be used in the treatment of inflammatory diseases of the human liver," says Timofey Zatsepin, professor at the Skoltech Center for Life Sciences.
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