Connexin32 deficiency exacerbates carbon tetrachloride-induced hepatocellular injury and liver fibrosis in mice

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Cogliati, Bruno ; Yanguas, Sara Crespo ; Da Silva, Tereza Cristina ; Arrais Aloia, Thiago Pinheiro ; Nogueira, Marina Sayuri ; Real-Lima, Mirela Aline ; Chaible, Lucas Martins ; Sanches, Daniel Soares ; Willebrords, Joost ; Maes, Michael ; Alves Pereira, Isabel Veloso ; de Castro, Inar Alves ; Vinken, Mathieu ; Zaidan Dagli, Maria Lucia

• Tipo de documento: Artigo Científico
• Fonte: TOXICOLOGY MECHANISMS AND METHODS; v. 26, n. 5, p. 9-pg., 2016-06-01.

Resumo

Objective: Liver fibrosis results from the perpetuation of the normal wound healing response to several types of injury. Despite the wealth of knowledge regarding the involvement of intracellular and extracellular signaling pathways in liver fibrogenesis, information about the role of intercellular communication mediated by gap junctions is scarce.Methods: In this study, liver fibrosis was chemically induced by carbon tetrachloride in mice lacking connexin32, the major liver gap junction constituent. The manifestation of liver fibrosis was evaluated based on a series of read-outs, including collagen morphometric and mRNA analysis, oxidative stress, apoptotic, proliferative and inflammatory markers.Results: More pronounced liver damage and enhanced collagen deposition were observed in connexin32 knockout mice compared to wild-type animals in experimentally triggered induced liver fibrosis. No differences between both groups were noticed in apoptotic signaling nor in inflammation markers. However, connexin32 deficient mice displayed decreased catalase activity and increased malondialdehyde levels.Conclusion: These findings could suggest that connexin32-based signaling mediates tissue resistance against liver damage by the modulation of the antioxidant capacity. In turn, this could point to a role for connexin32 signaling as a therapeutic target in the treatment of liver fibrosis. (AU)

• Processo FAPESP: 13/50420-6 - Canais de conexina e panexina como alvos terapêuticos e biomarcadores nas doenças hepáticas aguda e crônica
• Beneficiário: Mathieu Frederick Alexander Vinken
• Modalidade de apoio: Auxílio à Pesquisa - Programa SPEC
• Processo FAPESP: 05/59583-9 - Participação das conexinas 43 e 32 no desenvolvimento da fibrose hepática: estudo em camundongos geneticamente modificados
• Beneficiário: Bruno Cogliati
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 06/56138-7 - Avaliacao da importancia das conexinas 32 e 43 na cirrose hepatica induzida pela tioacetamida em camundongos.
• Beneficiário: Maria Lucia Zaidan Dagli
• Modalidade de apoio: Auxílio à Pesquisa - Regular