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

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Tiburcio, Tayna Cristina ; Willebrords, Joost ; da Silva, Tereza Cristina ; Alves Pereira, Isabel Veloso ; Nogueira, Marina Sayuri ; Yanguas, Sara Crespo ; Maes, Michael ; Silva, Elisangela dos Anjos ; Zaidan Dagli, Maria Lucia ; de Castro, Inar Alves ; Oliveira, Claudia Pinto ; Vinken, Mathieu ; Cogliati, Bruno

• Document type: Journal article
• Source: Clinical and experimental pharmacology & physiology; v. 44, n. 2, p. 10-pg., 2017-02-01.

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. (AU)

• FAPESP's process: 13/50420-6 - Connexin and pannexin channels as drug targets and biomarkers in acute and chronic liver disease
• Grantee: Mathieu Frederick Alexander Vinken
• Support Opportunities: Research Projects - SPEC Program