Connexin32 deficiency is associated with liver injury, inflammation and oxidative stress in experimental non-alcoholic steatohepatitis
Autor: | Claudia P. Oliveira, Maria Lúcia Zaidan Dagli, Sara Crespo Yanguas, Michaël Maes, Joost Willebrords, Elisangela dos Anjos Silva, Tereza Cristina da Silva, Maria do Socorro Nogueira, Inar Alves de Castro, Mathieu Vinken, Isabel Veloso Alves Pereira, Taynã Tiburcio, Bruno Cogliati |
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Přispěvatelé: | Pharmaceutical and Pharmacological Sciences, Connexin Signalling Research Group, Liver Connexin and Pannexin Research Group, Experimental in vitro toxicology and dermato-cosmetology |
Rok vydání: | 2017 |
Předmět: |
Male
0301 basic medicine Pathology Steatosis Physiology medicine.medical_treatment Oxidative Stress/genetics UP-REGULATION medicine.disease_cause Connexins Lipid Metabolism/genetics Liver/immunology Non-alcoholic Fatty Liver Disease oxidative stress Non-alcoholic steatohepatitis Mice Knockout Liver injury ESTRESSE OXIDATIVO Non-alcoholic Fatty Liver Disease/immunology Connexins/deficiency Gap Junctions Lipids Liver regeneration 3. Good health Liver Cytokines medicine.symptom Sterol Regulatory Element Binding Protein 1 Gap Junctions/metabolism Fatty Acid-Binding Proteins/genetics Fatty Acid Binding Protein 3 medicine.medical_specialty Inflammation Biology Fatty Acid-Binding Proteins Cytokines/blood Article connexin32 03 medical and health sciences Downregulation and upregulation Sterol Regulatory Element Binding Protein 1/genetics Physiology (medical) Internal medicine medicine Animals Pharmacology Lipids/blood Insulin Lipid Metabolism medicine.disease Liver Regeneration Mice Inbred C57BL 030104 developmental biology Endocrinology inflammation liver damage Steatohepatitis Oxidative stress |
Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
ISSN: | 0305-1870 |
DOI: | 10.1111/1440-1681.12701 |
Popis: | 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. |
Databáze: | OpenAIRE |
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