Polysialic acid/neural cell adhesion molecule modulates the formation of ductular reactions in liver injury

• DOI: 10.1002/hep.27099
• Publication Date: 2014-02-28T13:05:33Z
• Authors: Atsunori Tsuchiya; Wei-Yu Lu; Birgit Weinhold; Luke Boulter; Benjamin M. Stutc...; Michael J. Williams; Rachel V. Guest; Sarah E. Minnis-L...; Alison C. MacKinnon; David Schwarzer; Takafumi Ichida; Minoru Nomoto; Yutaka Aoyagi; Rita Gerardy-Schahn; Stuart J. Forbes
• Keywords: Polysialic acid

In severe liver injury, ductular reactions (DRs) containing bipotential hepatic progenitor cells (HPCs) branch from the portal tract. Neural cell adhesion molecule (NCAM) marks bile ducts and DRs, but not mature hepatocytes. NCAM mediates interactions between surrounding matrix; however, its role in development regeneration is undefined. Polysialic acid (polySia), a unique posttranslational modifier of NCAM, produced by enzymes, ST8SiaII ST8SiaIV, weakens interactions. The polySia with synthesizing enzymes ST8SiaIV were examined HPCs vivo using choline-deficient ethionine-supplemented 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet models injury regeneration, vitro proliferation, differentiation, migration, use mouse gene defects polysialyltransferases ( St8sia 2+/ −4+/ − , St8sia2− / −4− ). We show that, during development, required for correct formation because both St8sia2+/ mice) caused abnormal duct development. normal liver, there minimal production few NCAM+ cells. Subsequent to expand DRs/HPCs through ST8SiaIV. PolySia cell-cell cell-matrix interactions, facilitating HGF-induced migration. Differentiation hepatocytes results transcriptional down-regulation cleavage polySia-NCAM. Cleavage endosialidase (endoN) reduces migration DRs into parenchyma. Conclusion : modification ductules allowing migrate regeneration. Modulation levels may provide therapeutic option (Hepatology 2014;60:1727–1740)