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Effect of hypoxia on aquaporins and hepatobiliary transport systems in human hepatic cells
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Effect of hypoxia on aquaporins and hepatobiliary transport systems in human hepatic cells
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Journal Article
Effect of hypoxia on aquaporins and hepatobiliary transport systems in human hepatic cells
2025
Overview
Objectives
Hepatic ischemia and hypoxia are accompanied by reduced bile flow, biliary sludge and cholestasis. Hepatobiliary transport systems, nuclear receptors and aquaporins were studied after hypoxia and reoxygenation in human hepatic cells.
Methods
Expression of Aquaporin 8 (
AQP8
), Aquaporin 9 (
AQP9
), Pregnane X receptor (
PXR
), Farnesoid X receptor (
FXR
), Organic anion transporting polypeptide 1 (
OATP1
), and the Multidrug resistance-associated protein 4 (
MRP4
) were investigated in induced pluripotent stem cells (iPSCs) derived hepatic cells and the immortalized hepatic line HepG2. HepG2 was subjected to combined oxygen and glucose deprivation for 4 h followed by reoxygenation.
Results
Expression of
AQP8
and
AQP9
increased during differentiation in iPSC-derived hepatic cells. Hypoxia did not alter mRNA levels of
AQP8
, but reoxygenation caused a marked increase in
AQP8
mRNA expression. While expression of
OATP1
had a transient increase during reoxygenation,
MRP4
showed a delayed downregulation. Knock-down of FXR did not alter the expression of
AQP8
,
AQP9
,
MRP4
, or
OATP1
. Post-hypoxic protein levels of AQP8 were reduced after 68 h of reoxygenation compared to normoxic controls.
Conclusions
Post-transcriptional mechanisms rather than reduced transcription cause reduction in AQP8 protein concentration after hypoxia-reoxygenation in hepatic cells. Expression patterns differed between hepatobiliary transport systems during hypoxia and reoxygenation.
Impact
Expression of AQP8 and AQP9 increased during differentiation in induced pluripotent stem cells.
Expression of hepatobiliary transporters varies during hypoxia and reoxygenation.
Post-hypoxic protein levels of AQP8 were reduced after 68 h of reoxygenation.
Post-transcriptional mechanisms rather than reduced transcription cause reduction in AQP8 protein concentration after hypoxia-reoxygenation in hepatic cells.
Hypoxia and reoxygenation may affect aquaporins in hepatic cells and potentially affect bile composition.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
