Studies on a role of a crosslinking enzyme, transglutaminase in pathogenesis of liver diseases

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We demonstrated that upon injury, a protein crosslinking enzyme, transglutaminase translocates into the nucleus via its C-domain, crosslinks and inactivates Sp1 transcription factor, which results in the downregulation of the expression levels in c-Met, leading to caspase-independent hepatic cell death as well as fibrosis of the liver in both animal models and patients. We started screening of a unique compound that specifically inhibits nuclear translocation of transglutaminase.