title: Connexin32 deficiency is associated with liver injury, inflammation and oxidative stress in experimental non-alcoholic steatohepatitis.
abstract: Non-alcoholic steatohepatitis is a highly prevalent liver pathology featured by hepatocellular fat deposition and inflammation. Connexin32, which is the major building block of hepatocellular gap junctions, has a protective role in hepatocarcinogenesis and is downregulated in chronic liver diseases. However, the role of connexin32 in non-alcoholic steatohepatitis remains unclear. Connexin32-/-mice and their wild-type littermates were fed a choline-deficient high-fat diet. The manifestation of non-alcoholic steatohepatitis was evaluated based on a battery of clinically relevant read-outs, including histopathological examination, diverse indicators of inflammation and liver damage, in-depth lipid analysis, assessment of oxidative stress, insulin and glucose tolerance, liver regeneration and lipid-related biomarkers. Overall, more pronounced liver damage, inflammation and oxidative stress were observed in connexin32-/-mice compared to wild-type animals. No differences were found in insulin and glucose tolerance measurements and liver regeneration. However, two lipid-related genes, srebf1 and fabp3, were upregulated in Cx32-/-mice in comparison with wild-type animals. These findings suggest that connexin32-based signalling is not directly involved in steatosis as such, but rather in the sequelae of this process, which underlie progression of non-alcoholic steatohepatitis.
authors.affiliation: Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Taynã Cristina
authors.initials: TC
authors.lastname: Tiburcio
authors.affiliation: Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Joost
authors.initials: J
authors.lastname: Willebrords
authors.affiliation: Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Tereza Cristina
authors.initials: TC
authors.lastname: da Silva
authors.affiliation: Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Isabel Veloso Alves
authors.initials: IV
authors.lastname: Pereira
authors.affiliation: Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Marina Sayuri
authors.initials: MS
authors.lastname: Nogueira
authors.affiliation: Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Sara
authors.initials: S
authors.lastname: Crespo Yanguas
authors.affiliation: Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Michaël
authors.initials: M
authors.lastname: Maes
authors.affiliation: Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Elisangela Dos Anjos
authors.initials: ED
authors.lastname: Silva
authors.affiliation: Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Maria Lucia Zaidan
authors.initials: ML
authors.lastname: Dagli
authors.affiliation: Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Inar Alves
authors.initials: IA
authors.lastname: de Castro
authors.affiliation: Department of Gastroenterology, Clinical Division, Hepatology Branch, University of São Paulo School of Medicine, São Paulo, Brazil.
authors.forename: Cláudia Pinto
authors.initials: CP
authors.lastname: Oliveira
authors.affiliation: Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vinken
authors.affiliation: Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
authors.forename: Bruno
authors.initials: B
authors.lastname: Cogliati
mesh_terms: D000818:Animals; D017630:Connexins / Q000172:deficiency* / Q000235:genetics; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D017629:Gap Junctions / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D008055:Lipids / Q000097:blood; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D008115:Liver Regeneration; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000235:genetics; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D015854:Up-Regulation; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D016207:Cytokines; D000074026:Fatty Acid Binding Protein 3; D050556:Fatty Acid-Binding Proteins; D008055:Lipids; D051780:Sterol Regulatory Element Binding Protein 1; D000097002:Gap Junction beta-1 Protein; C493409:Fabp3 protein, mouse; C497388:Srebf1 protein, mouse
keywords: connexin32; inflammation; liver damage; non-alcoholic steatohepatitis; oxidative stress; steatosis