Adenovirus-mediated human aquaporin-1 expression in hepatocytes improves lipopolysaccharide-induced cholestasis

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dc.citation.titleIUBMB Life
dc.citation.volume69
dc.contributor.orcidhttp://orcid.org/0000-0003-2934-8863
dc.creatorMarrone, Julieta
dc.creatorDanielli, Mauro
dc.creatorGaspari, César Ismael
dc.creatorMarinelli, Raúl A.
dc.date.accessioned2024-08-02T14:14:53Z
dc.date.available2024-08-02T14:14:53Z
dc.date.issued2017-12
dc.description.abstractLipopolysaccharides (LPS) are known to cause cholestasis in sepsis. There is evidence that a defective expression of canalicular aquaporin water channels contributes to bile secretory failure in LPS-induced cholestasis. Thus, we studied whether the hepatic adenovirus-mediated transfer of human aquaporin-1 gene (haqp1) can improve the cholestasis induced by LPS. Adenoviral vector encoding hAQP1 (AdhAQP1) or control vector was administered to rats by retrograde intrabiliary infusion. Hepatocyte canalicular hAQP1 expression was assessed by liver immunostaining and immunoblotting in purified plasma membranes. LPS reduced bile flow and biliary bile acid excretion by 30% and 45%, respectively. AdhAQP1-treatment normalized both bile flow and biliary bile acid excretion in LPS-induced cholestasis. Moreover, markedly elevated serum bile acid levels in cholestatic rats, were also normalized with the AdhAQP1 hepatic transduction. Bile flow and serum or biliary bile acids in normal rats were not significantly altered by AdhAQP1. AdhAQP1 delivery unaffected the downregulated protein expression of canalicular bile salt export pump (BSEP/ABCB11) in cholestasis, but improved its transport activity restoring reduced canalicular cholesterol content. Our data suggest that the adenovirus-mediated hepatocyte hAQP1 expression improves LPS-induced cholestasis in rats by stimulating the BSEP/ABCB11-mediated biliary bile acid excretion; a finding that might contribute to the understanding and treatment of sepsis-associated cholestatic diseases.
dc.description.filFil: Marrone, Julieta. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental (IFISE-CONICET); Argentina.
dc.description.filFil: Danielli, Mauro. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental (IFISE-CONICET); Argentina.
dc.description.filFil: Gaspari, César Ismael. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental (IFISE-CONICET); Argentina.
dc.description.filFil: Marinelli, Raúl A. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental (IFISE-CONICET); Argentina.
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET): PIP2015‐088, PUE 0089
dc.description.sponsorshipAgencia Nacional de Promoción Científica y Tecnológica (ANPCyT): PICT 2015‐0439
dc.format.extent978-984
dc.identifier.issn1521-6543
dc.identifier.urihttps://hdl.handle.net/2133/27503
dc.language.isoen
dc.publisherJohn Wiley & Sons Inc
dc.relation.publisherversionhttps://doi.org/10.1002/iub.1689
dc.relation.publisherversionhttps://iubmb.onlinelibrary.wiley.com/doi/10.1002/iub.1689
dc.rightsopenAccess
dc.rights.holderInternational Union of Biochemistry and Molecular Biology
dc.rights.holderUniversidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas
dc.rights.textAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAquaporin-1
dc.subjectLPS-induced cholestasis
dc.subjectBiliary bile acidexcretion
dc.subjectGene transfer
dc.titleAdenovirus-mediated human aquaporin-1 expression in hepatocytes improves lipopolysaccharide-induced cholestasis
dc.typearticulo
dc.type.collectionarticulo
dc.type.versionpublishedVersion

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