Improved hepatic MRP2/ABCC2 transport activity in LPS-induced cholestasis by aquaporin-1 gene transfer

• Published in: Biochimie 2019-10, Vol.165, p.179-182
• Main Authors: Marrone, Julieta, Tocchetti, Guillermo N., Danielli, Mauro, Mottino, Aldo D., Marinelli, Raúl A.
• Format: Article
• Language: English
• Subjects: Adenoviral gene transfer; Animals; Aquaporin 1 - genetics; Aquaporin 1 - physiology; Aquaporin-1; ATP-Binding Cassette Transporters - metabolism; Bile - metabolism; Biliary glutathione excretion; Cholestasis - metabolism; Cholestasis - therapy; Cholestasis triggered by LPS; Gene Transfer Techniques; Hepatocytes - cytology; Hepatocytes - metabolism; Male; Multidrug resistance-associated protein-2; Rats, Wistar
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2019.07.027

Multidrug resistance-associated protein 2 (MRP2/ABCC2), a hepatocyte canalicular transporter involved in bile secretion, is downregulated in cholestasis triggered by lipopolysaccharide. The human aquaporin-1 (hAQP1) adenovirus-mediated gene transfer to liver improves cholestasis by incompletely defined mechanisms. Here we found that hAQP1 did not affect MRP2/ABCC2 expression, but significantly increased its transport activity assessed in situ with endogenous and exogenous substrates, likely by a hAQP1-induced increase in canalicular membrane cholesterol amount. Our results suggest that hAQP1-induced MRP2/ABCC2 activation contributes to the cholestasis improvement. •Hepatic gene transfer of human aquaporin-1 (hAQP1) improves LPS-induced cholestasis.•hAQP1 increases liver MRP2/ABCC2 transport activity without affecting its expression.•MRP2/ABCC2 activation would be due to hAQP1-increased canalicular cholesterol content.•hAQP1-induced MRP2/ABCC2 activation contributes to improve LPS cholestasis.