Protective effect of genetic deletion of pannexin1 in experimental mouse models of acute and chronic liver disease.

Autor: Willebrords J; Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium. Electronic address: joost.willebrords@vub.be., Maes M; Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium. Electronic address: michael.mc.maes@vub.be., Pereira IVA; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva 87, 05508-270 São Paulo, Brazil. Electronic address: isabelveloso@gmail.com., da Silva TC; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva 87, 05508-270 São Paulo, Brazil. Electronic address: terezacs@usp.br., Govoni VM; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva 87, 05508-270 São Paulo, Brazil. Electronic address: veronica.mgovoni@gmail.com., Lopes VV; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva 87, 05508-270 São Paulo, Brazil. Electronic address: valeria.veras95@gmail.com., Crespo Yanguas S; Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium. Electronic address: sara.crespo.yanguas@vub.ac.be., Shestopalov VI; Bascom Palmer Eye Institute, Department of Ophthalmology, University of Miami Miller School of Medicine, 1638 NW 10th Avenue, 33136 Miami, FL, United States. Electronic address: vshestopalov@miami.edu., Nogueira MS; Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 580, 05508-270 São Paulo, Brazil. Electronic address: masayuri.nogueira@gmail.com., de Castro IA; Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 580, 05508-270 São Paulo, Brazil. Electronic address: inar@usp.br., Farhood A; Department of Pathology, St. David's North Austin Medical Center, 601E 15th Street, 78701 Austin, United States. Electronic address: farhood.a.i@gmail.com., Mannaerts I; Department of Liver Cell Biology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium. Electronic address: inmannae@vub.ac.be., van Grunsven L; Department of Liver Cell Biology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium. Electronic address: lvgrunsv@vub.ac.be., Akakpo J; Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, 66160 Kansas City, United States. Electronic address: jakakpo@kumc.edu., Lebofsky M; Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, 66160 Kansas City, United States. Electronic address: mlebofsky@kumc.edu., Jaeschke H; Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, 66160 Kansas City, United States. Electronic address: hjaeschke@kumc.edu., Cogliati B; Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva 87, 05508-270 São Paulo, Brazil. Electronic address: bcogliati@usp.br., Vinken M; Department of In Vitro Toxicology and Dermato-Cosmetology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium. Electronic address: mvinken@vub.ac.be.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular basis of disease [Biochim Biophys Acta Mol Basis Dis] 2018 Mar; Vol. 1864 (3), pp. 819-830. Date of Electronic Publication: 2017 Dec 12.
DOI: 10.1016/j.bbadis.2017.12.013
Abstrakt: 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 48h or were fed a choline-deficient high-fat diet for 8weeks. 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 pannexin1 may play a role in the pathogenesis of liver disease.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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