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
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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