Transcription factor GATA6 in ductal metaplasia of hepatocytes

Abstract. GATA6 is evolutionary highly conserved transcription factor and a newish indicator and possible causer of ductal metaplasia in biliary atresia (BA). BA is a rare neonatal cholestatic liver disease caused by fibroinflammatory obstruction of bile ducts. BA causes proliferation of bile ducts which is also called ductal metaplasia. In ductal metaplasia hepatocytes phenotype starts resembling more cholangiocytes. When bile gathers inside the liver it (liver) starts to create new bile ducts. This reaction is called ductal reaction what is a consequence of ductal metaplasia. In this thesis work we, study the role of GATA6 in ductal metaplasia. We have two different kinds of mice: control mouse (ctrl) and knock out mouse (cKO). Both mice were operated with bile duct ligation (BDL) to resemble the BA-like condition. Our control (Ctrl) mouse only went over BDL and cKO mouse’s GATA6 gene was silenced in addition of the BDL. Missing of GATA6 has shown histology changes in liver tissue — there is no clear bile duct structure like in normal BA-like tissue. Post-mortem tells also a bad condition of the liver of cKO mouse. Similarly, gene expression studies supports hypothesis that ductal reaction hardly ever happens when GATA6 is missing