PMID- 30059007 OWN - NLM STAT- MEDLINE DCOM- 20190226 LR - 20190524 IS - 2050-084X (Electronic) IS - 2050-084X (Linking) VI - 7 DP - 2018 Jul 30 TI - Differential expression of Lutheran/BCAM regulates biliary tissue remodeling in ductular reaction during liver regeneration. LID - 10.7554/eLife.36572 [doi] LID - e36572 AB - Under chronic or severe liver injury, liver progenitor cells (LPCs) of biliary origin are known to expand and contribute to the regeneration of hepatocytes and cholangiocytes. This regeneration process is called ductular reaction (DR), which is accompanied by dynamic remodeling of biliary tissue. Although the DR shows apparently distinct mode of biliary extension depending on the type of liver injury, the key regulatory mechanism remains poorly understood. Here, we show that Lutheran (Lu)/Basal cell adhesion molecule (BCAM) regulates the morphogenesis of DR depending on liver disease models. Lu(+) and Lu(-) biliary cells isolated from injured liver exhibit opposite phenotypes in cell motility and duct formation capacities in vitro. By overexpression of Lu, Lu(-) biliary cells acquire the phenotype of Lu(+) biliary cells. Lu-deficient mice showed severe defects in DR. Our findings reveal a critical role of Lu in the control of phenotypic heterogeneity of DR in distinct liver disease models. CI - (c) 2018, Miura et al. FAU - Miura, Yasushi AU - Miura Y AD - Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. AD - Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan. FAU - Matsui, Satoshi AU - Matsui S AD - Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. AD - Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan. FAU - Miyata, Naoko AU - Miyata N AD - Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. FAU - Harada, Kenichi AU - Harada K AD - Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan. FAU - Kikkawa, Yamato AU - Kikkawa Y AD - Department of Clinical Biochemistry, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan. FAU - Ohmuraya, Masaki AU - Ohmuraya M AD - Department of Genetics, Hyogo College of Medicine, Hyogo, Japan. FAU - Araki, Kimi AU - Araki K AD - Institute of Resource Development and Analysis, Kumamoto University, Kumamoto, Japan. FAU - Tsurusaki, Shinya AU - Tsurusaki S AD - Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. AD - Laboratory of Stem Cell Regulation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan. FAU - Okochi, Hitoshi AU - Okochi H AD - Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. FAU - Goda, Nobuhito AU - Goda N AD - Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan. FAU - Miyajima, Atsushi AU - Miyajima A AD - Laboratory of Cell Growth and Differentiation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan. FAU - Tanaka, Minoru AU - Tanaka M AUID- ORCID: 0000-0003-2500-7973 AD - Department of Regenerative Medicine, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan. AD - Laboratory of Stem Cell Regulation, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180730 PL - England TA - Elife JT - eLife JID - 101579614 RN - 0 (BCAM protein, human) RN - 0 (Bcam protein, mouse) RN - 0 (Cell Adhesion Molecules) RN - 0 (Epithelial Cell Adhesion Molecule) RN - 0 (Integrin beta1) RN - 0 (Laminin) RN - 0 (Lutheran Blood-Group System) RN - 0 (Membrane Glycoproteins) RN - 0 (RNA, Messenger) RN - 0 (laminin alpha5) RN - N91BDP6H0X (Choline) SB - IM MH - Animals MH - Antibody Specificity/immunology MH - Bile Ducts/*metabolism/*physiology MH - Cell Adhesion Molecules/*metabolism MH - Cell Movement/genetics MH - Cell Separation MH - Choline MH - Diet MH - Disease Models, Animal MH - Epithelial Cell Adhesion Molecule/metabolism MH - Gene Expression Regulation MH - Humans MH - Integrin beta1/genetics/metabolism MH - Laminin/metabolism MH - Liver/metabolism MH - *Liver Regeneration/genetics MH - Lutheran Blood-Group System/*metabolism MH - Membrane Glycoproteins/genetics/*metabolism MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Models, Biological MH - Phenotype MH - RNA, Messenger/genetics/metabolism MH - Reproducibility of Results PMC - PMC6107333 OTO - NOTNLM OT - developmental biology OT - heterogeneity OT - mouse OT - progenitor OT - regeneration OT - regenerative medicine OT - remodeling OT - stem cells COIS- YM, SM, NM, KH, YK, MO, KA, ST, HO, NG, AM, MT No competing interests declared EDAT- 2018/07/31 06:00 MHDA- 2019/02/27 06:00 PMCR- 2018/07/30 CRDT- 2018/07/31 06:00 PHST- 2018/03/11 00:00 [received] PHST- 2018/07/28 00:00 [accepted] PHST- 2018/07/31 06:00 [pubmed] PHST- 2019/02/27 06:00 [medline] PHST- 2018/07/31 06:00 [entrez] PHST- 2018/07/30 00:00 [pmc-release] AID - 36572 [pii] AID - 10.7554/eLife.36572 [doi] PST - epublish SO - Elife. 2018 Jul 30;7:e36572. doi: 10.7554/eLife.36572.