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Connexin32 deficiency is associated with liver injury, inflammation and oxidative stress in experimental non‐alcoholic steatohepatitis
Author(s) -
Tiburcio Taynã Cristina,
Willebrords Joost,
Silva Tereza Cristina,
Pereira Isabel Veloso Alves,
Nogueira Marina Sayuri,
Crespo Yanguas Sara,
Maes Michaël,
Silva Elisangela dos Anjos,
Dagli Maria Lucia Zaidan,
Castro Inar Alves,
Oliveira Cláudia Pinto,
Vinken Mathieu,
Cogliati Bruno
Publication year - 2017
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/1440-1681.12701
Subject(s) - steatohepatitis , steatosis , fatty liver , inflammation , oxidative stress , liver injury , medicine , endocrinology , pathology , disease
Summary 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.