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Connexin32 deficiency is associated with liver injury, inflammation and oxidative stress in experimental non-alcoholic steatohepatitis

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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.

Tijdschrift: Clinical & Experimental Pharmacology & Physiology
ISSN: 0305-1870
Issue: 2
Volume: 44
Pagina's: 197-206
Jaar van publicatie:2017
Trefwoorden:connexin32, inflammation, liver damage, non-alcoholic steatohepatitis, oxidative stress, steatosis, Sterol Regulatory Element Binding Protein 1/genetics, Non-alcoholic Fatty Liver Disease/immunology, Up-Regulation, Liver Regeneration, Mice, Inbred C57BL, Male, Fatty Acid-Binding Proteins/genetics, Cytokines/blood, Gap Junctions/metabolism, Mice, Knockout, Oxidative Stress/genetics, Animals, Connexins/deficiency, Fatty Acid Binding Protein 3, Lipid Metabolism/genetics, Liver/immunology, Lipids/blood
CSS-citation score:1
Auteurs:International