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

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. [ABSTRACT FROM AUTHOR]