title: The functional interrelationship between gap junctions and fenestrae in endothelial cells of the liver organoid.
abstract: Functional intact liver organoid can be reconstructed in a radial-flow bioreactor when human hepatocellular carcinoma (FLC-5), mouse immortalized sinusoidal endothelial M1 (SEC) and A7 (HSC) hepatic stellate cell lines are cocultured. The structural and functional characteristics of the reconstructed organoid closely resemble the in vivo liver situation. Previous liver organoid studies indicated that cell-to-cell communications might be an important factor for the functional and structural integrity of the reconstructed organoid, including the expression of fenestrae. Therefore, we examined the possible relationship between functional intact gap junctional intercellular communication (GJIC) and fenestrae dynamics in M1-SEC cells. The fine morphology of liver organoid was studied in the presence of (1) irsogladine maleate (IM), (2) oleamide and (3) oleamide followed by IM treatment. Fine ultrastructural changes were studied by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and compared with control liver organoid data. TEM revealed that oleamide affected the integrity of cell-to-cell contacts predominantly in FLC-5 hepatocytes. SEM observation showed the presence of fenestrae on M1-SEC cells; however, oleamide inhibited fenestrae expression on the surface of endothelial cells. Interestingly, fenestrae reappeared when IM was added after initial oleamide exposure. GJIC mediates the number of fenestrae in endothelial cells of the liver organoid.
authors.affiliation: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. masayas@jikei.ac.jp
authors.forename: Masaya
authors.initials: M
authors.lastname: Saito
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Matsuura
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nagatsuma
authors.forename: Ken
authors.initials: K
authors.lastname: Tanaka
authors.forename: Haruka
authors.initials: H
authors.lastname: Maehashi
authors.forename: Keiko
authors.initials: K
authors.lastname: Shimizu
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Hataba
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Kato
authors.forename: Isao
authors.initials: I
authors.lastname: Kashimori
authors.forename: Hisao
authors.initials: H
authors.lastname: Tajiri
authors.forename: Filip
authors.initials: F
authors.lastname: Braet
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009829:Oleic Acids / Q000494:pharmacology; D009940:Organoids
chemical_list: D009829:Oleic Acids; C029407:oleylamide