SgIGSF is a novel biliary-epithelial cell adhesion molecule mediating duct/ductule development.
Spermatogenic immunoglobulin superfamily (SgIGSF) is an intercellular adhesion molecule of the nectin-like family. While screening its tissue distribution, we found that it was expressed in fetal liver but not adult liver. In the present study, we examined which cells in developing and regenerating liver express SgIGSF via immunohistochemistry and Western blot analysis. In developing mouse liver, SgIGSF expression was transiently upregulated at perinatal ages and was restricted to the lateral membrane of biliary epithelial cells (BECs). In regenerating rat livers from the 2-acetylaminofluorene/partial hepatectomy model, SgIGSF was detected exclusively in oval cells that aligned in ductal and trabecular patterns by the second week posthepatectomy. In human livers, fetal and newborn bile ducts and cirrhotic bile ductules were clearly positive for SgIGSF, whereas disease-free adult bile ducts were negative. To investigate the role of SgIGSF in bile duct/ductule formation, we used an in vitro model in which rat hepatocyte aggregates embedded in collagen gels containing insulin and epidermal growth factor extend epithelial sheets and processes in the first week and form ductules within a month. The process and ductular cells were continuously positive for SgIGSF and cytokeratin 19, a BEC marker. When the aggregate culture was started in the presence of a function-blocking anti-SgIGSF antibody, the number of epithelial processes per aggregate was reduced by 80%.


CONCLUSIONS
We propose that SgIGSF is a novel and functional BEC adhesion molecule that is expressed for a limited time during active bile duct/ductule formation.
Ito
Akihiko
A
Division of Surgical Pathology, Kobe University Graduate School of Medicine, Kobe, Hyogo, Japan. akito@med.kobe-u.ac.jp
Nishikawa
Yuji
Y
Ohnuma
Kazuhiro
K
Ohnuma
Ikuyo
I
Koma
Yu-ichiro
Y
Sato
Ayuko
A
Enomoto
Katsuhiko
K
Tsujimura
Tohru
T
Yokozaki
Hiroshi
H
D000818:Animals; D001652:Bile Ducts / Q000196:embryology* / Q000254:growth & development* / Q000502:physiology; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000502:physiology*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000502:physiology*; D053539:Keratin-19 / Q000235:genetics / Q000502:physiology; D008115:Liver Regeneration / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D011916:Rats, Inbred F344; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology
C403514:CADM1 protein, human; C498598:Cadm1 protein, mouse; C465040:Cadm1 protein, rat; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D007136:Immunoglobulins; D053539:Keratin-19; D008565:Membrane Proteins; D025521:Tumor Suppressor Proteins