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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Genetic ablation of pannexin1 counteracts liver fibrosis in a chemical, but not in a surgical mouse model

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Autor(es):
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Yanguas, Sara Crespo [1] ; da Silva, Tereza C. [2] ; Pereira, Isabel V. A. [2] ; Maes, Michael [1] ; Willebrords, Joost [1] ; Shestopalov, Valery I. [3, 4] ; Goes, Bruna M. [2] ; Nogueira, Marina Sayuri [5] ; de Castro, Inar Alves [5] ; Romualdo, Guilherme R. [6] ; Barbisan, Luis F. [6] ; Gijbels, Eva [1] ; Vinken, Mathieu [1] ; Cogliati, Bruno [2]
Número total de Autores: 14
Afiliação do(s) autor(es):
[1] Vrije Univ Brussel, Dept In Vitro Toxicol & Dermatocosmetol, Brussels - Belgium
[2] Univ Sao Paulo, Sch Vet Med & Anim Sci, Dept Pathol, Sao Paulo - Brazil
[3] Univ Miami, Miller Sch Med, Dept Ophthalmol, Bascom Palmer Eye Inst, Miami, FL 33136 - USA
[4] Univ Miami, Miller Sch Med, Dept Cell Biol & Anat, Miami, FL 33136 - USA
[5] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Food & Expt Nutr, Sao Paulo - Brazil
[6] UNESP Sao Paulo State Univ, Botucatu Med Sch, Dept Pathol, Botucatu, SP - Brazil
Número total de Afiliações: 6
Tipo de documento: Artigo Científico
Fonte: ARCHIVES OF TOXICOLOGY; v. 92, n. 8, p. 2607-2627, AUG 2018.
Citações Web of Science: 4
Resumo

Liver fibrosis is the final common pathway for almost all causes of chronic liver injury. This chronic disease is characterized by excessive deposition of extracellular matrix components mainly due to transdifferentiation of quiescent hepatic stellate cell into myofibroblasts-like cells, which in turn is driven by cell death and inflammation. In the last few years, paracrine signaling through pannexin1 channels has emerged as a key player in the latter processes. The current study was set up to investigate the role of pannexin1 signaling in liver fibrosis. Wild-type and whole body pannexin1 knock-out mice were treated with carbon tetrachloride or subjected to bile duct ligation. Evaluation of the effects of pannexin1 deletion was based on a number of clinically relevant read-outs, including markers of liver damage, histopathological analysis, oxidative stress, inflammation and regenerative capacity. In parallel, to elucidate the molecular pathways affected by pannexin1 deletion as well as to mechanistically anchor the clinical observations, whole transcriptome analysis of liver tissue was performed. While pannexin1 knock-out mice treated with carbon tetrachloride displayed reduced collagen content, hepatic stellate cell activation, inflammation and hepatic regeneration, bile duct ligated counterparts showed increased hepatocellular injury and antioxidant enzyme activity with a predominant immune response. Gene expression profiling revealed a downregulation of fibrotic and immune responses in pannexin1 knock-out mice treated with carbon tetrachloride, whereas bile duct ligated pannexin1-deficient animals showed a pronounced inflammatory profile. This study shows for the first time an etiology-dependent role for pannexin1 signaling in experimental 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
Linha de fomento: Auxílio à Pesquisa - Programa SPEC
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
Linha de fomento: 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
Linha de fomento: Bolsas no Brasil - Pós-Doutorado