Evidence map›Paper›PMID 38951656›Full record

ArticlePediatric research2025

Effect of hypoxia on aquaporins and hepatobiliary transport systems in human hepatic cells.

Niklas Starck Westerberg, Monica Atneosen-Åsegg, Maria Melheim, Maria Eugenia Chollet, Sean P Harrison, Richard Siller, Gareth J Sullivan, Runar Almaas

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Article in Pediatric research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Niklas Starck WesterbergDepartment of Pediatric Research, Oslo University Hospital, Oslo, Norway.
Monica Atneosen-ÅseggInstitute of Clinical Medicine, University of Oslo, Oslo, Norway.
Maria MelheimDepartment of Pediatric Research, Oslo University Hospital, Oslo, Norway.
Maria Eugenia CholletInstitute of Clinical Medicine, University of Oslo, Oslo, Norway.
Sean P HarrisonDepartment of Pediatric Research, Oslo University Hospital, Oslo, Norway.
Richard SillerDepartment of Molecular Medicine, University of Oslo, Oslo, Norway.
Gareth J SullivanDepartment of Pediatric Research, Oslo University Hospital, Oslo, Norway.
Runar AlmaasDepartment of Pediatric Research, Oslo University Hospital, Oslo, Norway. runar.almaas@ous-hf.no.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesHepatic 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.

methodsExpression 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.

resultsExpression 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.

conclusionsPost-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.

Indexed as

AquaporinsHepatocytesHypoxiaLiverATP-Binding Cassette, Sub-Family C ProteinsBiological TransportCell DifferentiationCell HypoxiaHep G2 CellsHumansInduced Pluripotent Stem CellsPregnane X ReceptorReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearReceptors, SteroidRNA, MessengerABCC4 protein, humanAQP9 protein, humanaquaporin 8AquaporinsATP-Binding Cassette, Sub-Family C ProteinsPregnane X ReceptorReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearReceptors, SteroidRNA, Messenger

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.