Biliary elimination of cholesterol can be modulated by hepatocyte mitochondrial Aquaporin-8 in mice

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dc.citation.titleScientific Reports
dc.citation.volume16(1)
dc.creatorCapitani, María Celeste
dc.creatorCapiglioni, Alejo M.
dc.creatorMarinelli, Raúl A.
dc.creatorMarrone, Julieta
dc.date.accessioned2026-03-26T19:46:56Z
dc.date.available2026-03-26T19:46:56Z
dc.date.issued2026-02-06
dc.description.abstractSterol regulatory element-binding protein (SREBP) transcription factors directly or indirectly regulate key genes involved in hepatic cholesterol homeostasis, including biliary elimination. The ATP-binding cassette transporter G5 (ABCG5), located in hepatocyte canalicular plasma membranes, strongly controls the excretion of unesterified cholesterol into bile. Recently, we demonstrated in cultured hepatocytes that mitochondrial aquaporin-8 (mtAQP8), a channel protein capable of conducting H2O2, is involved in SREBP-controlled cholesterol synthesis. In this study, we evaluated whether hepatic mtAQP8 participates in modulating the biliary elimination of cholesterol. Using C57BL/6 mice, we found that adenovirus-induced mtAQP8 knockdown significantly downregulated the expression of sterol regulatory element-binding protein-2 (SREBP-2) and, through liver X receptor (LXR), that of ABCG5, which in turn decreased biliary cholesterol excretion. In contrast, mice with adenovirusmediated mitochondrial human AQP8 (hAQP8) expression significantly increased the expressions of SREBP-2, LXR, and ABCG5 and, consequently, the biliary excretion of cholesterol. A mitochondrialtargeted antioxidant, which has been shown to quench mitochondrial H2O2 release, did not affect mitochondrial hAQP8 expression, but prevented upregulation of SREBP-2, ABCG5, and biliary cholesterol excretion. Our data further support the involvement of mtAQP8 in hepatic cholesterol metabolism, suggesting that it modulates biliary cholesterol elimination through ABCG5 gene expression.
dc.description.filFil: Capitani, María Celeste. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental (IFISE-CONICET); Argentina.
dc.description.filFil: Capiglioni, Alejo M. 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.filFil: Marrone, Julieta. 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): PIBAA28720210100174
dc.description.sponsorshipAgencia Nacional de Promoción Científica y Tecnológica (ANPCyT): PICT 2018–02643
dc.description.sponsorshipConsejo Nacional de Investigaciones Científicas y Técnicas (CONICET): PIP 11220210100078CO
dc.description.versionpeerreviewed
dc.format.extent1-13
dc.identifier.citationCapitani, M.C., Capiglioni, A.M., Marinelli, R.A. et al. Biliary elimination of cholesterol can be modulated by hepatocyte mitochondrial Aquaporin-8 in mice. Sci Rep 16, 7579 (2026). https://doi.org/10.1038/s41598-026-39058-
dc.identifier.issn2045-2322
dc.identifier.urihttps://hdl.handle.net/2133/32694
dc.language.isoen
dc.publisherNature Research
dc.relation.publisherversionhttps://www.nature.com/articles/s41598-026-39058-6#article-info
dc.relation.publisherversionhttps://doi.org/10.1038/s41598-026-39058-6
dc.rightsopenAccess
dc.rights.holderCapitani, María Celeste
dc.rights.holderCapiglioni, Alejo M.
dc.rights.holderMarinelli, Raúl A.
dc.rights.holderMarrone, Julieta
dc.rights.holderUniversidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas
dc.rights.textAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectBiliary cholesterol excretion
dc.subjectMitochondrial aquaporin-8
dc.subjectABCG5
dc.subjectAdenovirus
dc.subjectHydrogen peroxide
dc.titleBiliary elimination of cholesterol can be modulated by hepatocyte mitochondrial Aquaporin-8 in mice
dc.typearticulo
dc.type.collectionarticulo
dc.type.versionpublishedVersion

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