Protective effect of genetic deletion of pannexinl in experimental mouse models of acute and chronic liver disease

Autor(es):Mostrar menos -

Willebrords, Joost ^[1] ; Maes, Michael ^[1] ; Alves Pereira, Isabel Veloso ^[2] ; da Silva, Tereza Cristina ^[2] ; Govoni, Veronica Mollica ^[2] ; Lopes, Valeria Veras ^[2] ; Yanguas, Sara Crespo ^[1] ; Shestopalov, Valery I. ^[3] ; Nogueira, Marina Sayuri ^[4] ; de Castro, Inar Alves ^[4] ; Farhood, Anwar ^[5] ; Mannaerts, Inge ^[6] ; van Grunsven, Leo ^[6] ; Akakpo, Jephte ^[7] ; Lebofsky, Margitta ^[7] ; Jaeschke, Hartmut ^[7] ; Cogliati, Bruno ^[2] ; Vinken, Mathieu ^[1]

Afiliação do(s) autor(es)

^[1] Vrije Univ Brussel, Fac Med & Pharm, Dept In Vitro Toxicol & Dermatocosmetol, Laarbeeklaan 103, B-1090 Brussels - Belgium

^[2] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, Ave Prof Dr Orlando Marques de Paiva 87, BR-05508270 Sao Paulo - Brazil

^[3] Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, 1638 NW 10th Ave, Miami, FL 33136 - USA

^[4] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Food & Expt Nutr, Ave Prof Linea Prestes 580, BR-05508270 Sao Paulo - Brazil

^[5] St Davids North Austin Med Ctr, Dept Pathol, 601E 15th St, Austin, TX 78701 - USA

^[6] Vrije Univ Brussel, Fac Med & Pharm, Dept Liver Cell Biol, Laarbeeklaan 103, B-1090 Brussels - Belgium

^[7] Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, 3901 Rainbow Blvd, Kansas City, KS 66160 - USA

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE; v. 1864, n. 3, p. 819-830, MAR 2018.
• Citações Web of Science: 5

Resumo

Pannexins are transmembrane proteins that form communication channels connecting the cytosol of an individual cell with its extracellular environment. A number of studies have documented the presence of pannexin1 in liver as well as its involvement in inflammatory responses. In this study, it was investigated whether pannexin1 plays a role in acute liver failure and non-alcoholic steatohepatitis, being prototypical acute and chronic liver pathologies, respectively, both featured by liver damage, oxidative stress and inflammation. To this end, wild-type and pannexin1(-/-) mice were overdosed with acetaminophen for 1, 6, 24 or 48 h or were fed a choline-deficient high-fat diet for 8 weeks. Evaluation of the effects of genetic pannexin1 deletion was based on a number of clinically relevant read-outs, including markers of liver damage, histopathological analysis, lipid accumulation, protein adduct formation, oxidative stress and inflammation. In parallel, in order to elucidate molecular pathways affected by pannexin1 deletion as well as to mechanistically anchor the clinical observations, whole transcriptome analysis of liver tissue was performed. The results of this study show that pannexin1(-/-) diseased mice present less liver damage and oxidative stress, while inflammation was only decreased in pannexin1(-/-) mice in which non-alcoholic steatohepatitis was induced. A multitude of genes related to inflammation, oxidative stress and xenobiotic metabolism were differentially modulated in both liver disease models in wild-type and in pannexin1(-/-) mice. Overall, the results of this study suggest that pannexinl may play a role in the pathogenesis of liver disease. (AU)

• Processo FAPESP: 14/23887-3 - Canais de conexina e panexina como alvos terapêuticos e biomarcadores nas doenças hepáticas aguda e crônica
• Beneficiário: Tereza Cristina da Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/23890-4 - Canais de conexina e panexina como alvos terapêuticos e biomarcadores nas doenças hepáticas aguda e crônica
• Beneficiário: Isabel Veloso Alves Pereira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• 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: 16/03579-8 - Canais de conexina e panexina como alvos terapêuticos e biomarcadores nas doenças hepáticas aguda e crônica
• Beneficiário: Valéria Veras Lopes
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica