title: Histological alterations in the livers of Cx43-deficient mice submitted to a cholestasis model.
abstract: Gap junction intercellular communication capacity and connexin expression are reportedly involved in cell proliferation. To understand the participation of connexins in biliary duct hyperplasia, a cholestasis model was applied to mice with heterologous deletion of Gja 1, the connexin 43 (Cx43) gene. Heterozygous (Cx43+/-) knockout (KO) and wild-type mice (Cx43+/+) (WT) were submitted to bile duct ligation and euthanized at different time points (48 h, 7 days, and 14 days) after surgery. After euthanasia, the macroscopic and microscopic liver alterations were examined. A histomorphometric study of the livers was performed. For this purpose, a grid containing 100 points was applied to each liver section. The volumetric fraction of bile ducts, hepatocytes, arterioles, and terminal hepatic vein were quantified. Cell proliferation was also quantified by western blot PCNA. High mortality was observed in both genotypes. The heterologous deletion of Cx43 did not affect the biliary duct hyperplasia or most of the other parameters analyzed; however, the Cx43-deficient mice showed decrease in hepatic vein angiogenesis in comparison with the wild-type mice 48 h after surgery. In conclusion, our results indicate that the Cx43 gene heterologous deletion does not affect the biliary duct hyperplasia; on the other hand, connexin 43 deficiencies do affect the hepatic vein angiogenesis, although other studies to understand the details of this influence will be necessary.
authors.affiliation: Laboratory of Experimental Oncology, Department of Pathology, Faculty of Veterinary Medicine and Animal Sciences, University of São Paulo, Brazil.
authors.forename: Tarso Felipe
authors.initials: TF
authors.lastname: Teixeira
authors.forename: Tereza Cristina
authors.initials: TC
authors.lastname: da Silva
authors.forename: Heidge
authors.initials: H
authors.lastname: Fukumasu
authors.forename: Cynthia Esteves
authors.initials: CE
authors.lastname: de Lima
authors.forename: Maria
authors.initials: M
authors.lastname: Lúcia Zaidan Dagli
authors.forename: José Luiz
authors.initials: JL
authors.lastname: Guerra
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation; D002779:Cholestasis / Q000378:metabolism* / Q000473:pathology; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism
chemical_list: D018031:Connexin 43; D018809:Proliferating Cell Nuclear Antigen