Tannic acid inhibits cholangiocyte proliferation after bile duct ligation via a cyclic adenosine 5′,3′-monophosphate-dependent pathway

Silvia Taffetani, Yoshiyuki Ueno, Fanyin Meng, Julie Venter, Heather Francis, Shannon Glaser, Gianfranco Alpini, Tushar Patel

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Chronic cholestatic diseases are characterized by morphological changes involving cholangiocyte proliferation and functional alterations of secretory capacity. The plant polyphenol tannic acid inhibits the growth of malignant human cholangiocytes. However, the mechanisms by which tannic acid limits excessive cholangiocyte proliferation are unknown. In this study we assessed the effect of tannic acid on cholangiocyte proliferation after bile duct ligation in rats. Tannic acid feeding decreased cholangiocyte proliferation and ductal mass in vivo after bile duct ligation. These changes were associated with functional changes in bile secretion and with decreases of intracellular cyclic adenosine 5′,3′-monophosphate. The anti-proliferative effect of tannic acid was associated with a reduction of ERK1,2 phosphorylation. Additionally, tannic acid feeding decreased protein kinase A phosphorylation and activity. Similar changes were observed in isolated cholangiocytes during in vitro incubation with tannic acid. Furthermore, forskolin abolished the anti-proliferative effect of tannic acid on cholangiocyte proliferation after bile duct ligation. In conclusion, the anti-proliferative effects of tannic acid in cholangiocytes involve modulation of ERK1,2 by a cyclic adenosine 5′,3′-monophosphate-protein kinase A-dependent pathway. These data suggest that tannic acid may be useful in limiting excessive cholangiocyte proliferation and modulating secretion during cholestasis.

Original languageEnglish (US)
Pages (from-to)1671-1679
Number of pages9
JournalAmerican Journal of Pathology
Volume166
Issue number6
DOIs
StatePublished - Jun 2005

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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