Evaluation of transglutaminase expression in the hepatobiliary tract

INTRODUCTION/OBJECTIVES: Transglutaminases [1] are an enzymatic family widely present in different tissues. New insights showed that transglutaminase type 2 (TG2) plays a pivotal role in several human diseases as liver fibrosis and viral hepatitis. Although the relevant pathogenetic involvement, its hepatic metabolism and homeostasis are not clearly understood. AIMS & METHODS: Our aim was to investigate in a combined model (in vitro and ex vivo) the presence and expression of TG2 in the human hepatobiliary tract. We studied TG2 expression in cell cultures of hepatocytes (Hep-G2) and cholangiocytes (SK-CHA-1 and MZ-CHA-1), with and without the choleretic stimulation of bile acid (glycochenodeoxycholic acid 0.5, 0.75mM for 48 hours) and in human bile from endoscopic retrograde cholangiographic catheterism (7 patients, 4M, mean age 47). We evaluated in cell lysates or culture medium TG2 protein (western blot), its activity (colorimetric assay) and expression of tissue transglutaminase mRNA (RT-PCR). Moreover, in human bile the presence of FXIII has been investigated (immunologic test).We found TG2 presence and activity in hepatocytes and cholangiocyets cell lines. The treatment with bile acid at non-toxic concentrations increased the expression and activity of TG2 in all the cell lines (from +20 to +40% vs. untreated cultures). TG activity was present in the medium of Hep-G2 cells but not in the medium of cholangiocytes cell lines. The base line expression is significantly higher in cholangiocytes compared to hepatocytes. A TG2 activity was demonstrated in hepatocytes cell culture medium and not in the cholangiocytes one; moreover a transglutaminasic activity was demonstrated in human bile (0.25±0.12 mU/ml) associated with the presence of the FXIII. CONCLUSION: Our preliminary in vitro data demonstrates that TG2 is represented in Hep-G2, SK-CHA-1 and MZ-CHA-1 human hepatic/biliary cell lines and in human bile. The treatment with bile acid in cell cultures increases its expression, suggesting a possible homeostatic regulation. REFERENCE(S): [1] Elli et al. Dig Liv Dis 2009; 41(8): 541−50. Disclosure of Interest: None Declared