Inhibition of Enzyme NOX4 Prevents Liver Fibrosis than TGF-beta
Liver fibrosis is an illness caused by the overproduction of extracellular matrix proteins in the liver tissue. NOX4, a family member of NADPH oxidase enzyme,plays an important role in liver fibrosis by inhibiting it. TGF-beta, a complex cytokine, the transforming growth factor-beta, involves in the fibrosis of liver.
Researchers at the Bellvitge Biomedical Research Institute (IDIBELL) and research group of Wolfgang Mikulitsat the Cancer Research Institute of the Medical University of Vienna (Austria)have led a study related to liver fibrosis and the result was published in PLoS One.In the research, they studied the function of TGF-beta in the pathophysiology of the liver.And they aimed to analyze routes below TGF-beta, i.e. the cytokine-induced pathways that may be responsible for the process leading to the occurrence of fibrosis, cell activation and production of extracellular matrix and the hepatocytes death.
Though several laboratories are studying the routes below the TGF-beta that mediate the fibrotic process to maintain other processes induced by TGF-beta to inhibit the tumor formation, the IDIBELL research group, firstly, has demonstrated that a family member of the enzymes involved in oxidation, the NOX4, which acts in the TGF-beta pathway, plays an important role in fibrosis in both in vivo in fibrotic experimental models mouse, and in vitro with culture cells. "Cancelling NOX4 prevents both activation of extracellular matrix producing cells and hepatocyte death," concluded the IDIBELL researcher.
As we know, during fibrosis, levels of TGF-beta are increased, and there is an activation of the extracellular matrix producing the activation of protecting cells of the extracellular matrix and other possible events leading to the death of hepatocytes.In early stages of tumor formation, TGF betais a prominent tumor suppressor but, in advanced stages, the cells adapt to escape from the growth inhibitory signals and potentiate tumor progression contributing to metastasiswhich means there could be this scene if we give anti-TGF beta for liver fibrosis patient: it indeed relieves the liver fibrosis, but the tumor factors rampage which may contribute to the increase probability of developing tumors.
The study also foundhigh level of NOX4 in samples from patients at different stages of fibrosis caused by infection with hepatitis C virus. Currently there are some NOX4 inhibitors drugs, so the study indicates its clinical potential and explains how they might act if they are used as a treatment in patients with hepatic fibrosis.
Tags: Enzyme NOX4, TGF-beta, Cytokine, Liver Fibrosis