Secondary bile acids and the biliary epithelia: The good and the bad

Table 2 Main findings regarding secondary bile acids and biliary epithelia

Model	Administration route	Main results	Main molecular, immunologic findings	Ref.
Ursodeoxycholic acid
BDL rat	Feeding (both the unconjugated and taurine-conjugated form)	Decreased biliary proliferation and secretion. No apoptosis	Decreased H3-histone. PCNA, SR and ASBT expression. No apoptosis. Increased PKC α expression	[38,39]
BDL + vagotomy rat	Feeding (both unconjugated and taurine-conjugated form)	Reversal of duct loss and apoptosis induced by vagotomy	PKCα/Ca2+ dependent mechanism	[41]
Mdr2(-/-) mice	Feeding	Decreased proliferation, inflammation and fibrosis	Inhibition of mast cells activity	[43]
Lithocolic acid
Mouse	Feeding	Destructive cholangitis, bile duct stenosis, bilary infarcts	Damage related to direct toxic effect and not to neutrophil infiltration	[52,53]
In vivo rat and isolated cholagiocytes	Feeding (cholic acid or Lithocholic acid both taurine conjugated)	Similar effect in increasing proliferation and secretion	Effect restricted to large cholangiocytes	[54,55]
In vivo rat and isolated cholagiocytes	Feeding (cholic acid or Lithocholic acid both taurine conjugated)	Cholangiocytes proliferation	Dependent by PKA-mediated ASBT expression	[56]
Deoxycholic acid
Human gallbladder cancer (specimens and cell lines)	In vitro exposure	Increased concentration associated with inhibition of tumor growth	Reduced miR-92b-3p inhibits PI3K/AKT activity	[60]

ASBT: Apical sodium bile acids transporter; BDL: Bile duct ligated; PCNA: Protein cellular nuclear antigen; SR: Secretin receptor.