Bile acid feeding increased proliferative activity and apical bile acid transporter expression in both small and large rat cholangiocytes

Bile acids (BA) enter cholangiocytes by the Na+-dependent apical BA transpo rter (ABAT). By this mechanism, taurocholate (TC) and taurolithocholate (TL C) increase cholangiocyte proliferation. No in vivo studies exist regarding the anatomical sites involved in BA-regulation of cholangiocyte growth. Sp ecific cholangiocyte subpopulations participate in BA-regulated proliferati on. Proliferation was assessed in liver sections by determining the number of proliferating cellular nuclear antigen (PCNA)-positive cholangiocytes an d cytokeratin-19 (CK-19)-positive ducts. We isolated small and large cholan giocytes from rats fed for I week TC, TLC, or BA control diet and determine d PCNA and ABAT expression and BA transport activity. We evaluated if TC an d TLC induction of ABAT expression was dependent on activation of PKC alpha . DNA replication was active only in large normal cholangiocytes. TC and TL C feeding increased proliferation of large cholangiocytes, induced the dc n ovo activation of proliferation of small cholangiocytes, overexpression of ABAT and BA transport activity in large cholangiocytes, and de novo express ion of ABAT and BA transport activity in small cholangiocytes. BA-stimulate d ABAT expression was dependent on PKC activation in cholangiocytes. TC and TLC stimulate proliferation of small and large cholangiocytes associated w ith PKC-dependent up-regulation of ABAT.