ArticleLiver international : official journal of the International Association for the Study of the Liver2017
Impaired N-linked glycosylation of uptake and efflux transporters in human non-alcoholic fatty liver disease.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 90 citations in OpenAlex.
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- Presence of Legacy and Emerging PFAS in Human Liver Specimens Banked in the United States from 2000 to 2024.Environmental science & technology · 2026Article
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- Effects of Chronic Elevation in Plasma Membrane Cholesterol on the Function of Human NaLivers · 2025Article
- Heart rate variability in the clinical assessment of patients with chronic liver disease.World journal of hepatology · 2025Review
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- Organic anion transporting polypeptides: Pharmacology, toxicology, structure, and transport mechanisms.Pharmacological reviews · 2025Review
- HFD-induced Alterations in Renal Tubular Oatp4c1-P-gp Transport Systems in Mice: Impact on Digoxin Renal Excretion and Gadolinium-Enhanced Radiological Manifestations.Current drug metabolism · 2025Article
- Chitinase-1 inhibition attenuates metabolic dysregulation and restores homeostasis in MASH animal models.Frontiers in immunology · 2025Article
- Nonalcoholic steatohepatitis increases plasma retention of sorafenib-glucuronide in a mouse model by altering hepatocyte hopping.Acta pharmaceutica Sinica. B · 2024Article
- Protein posttranslational modifications in metabolic diseases: basic concepts and targeted therapies.MedComm · 2024Review
- Pharmacokinetic Effects of Different Models of Nonalcoholic Fatty Liver Disease in Transgenic Humanized OATP1B Mice.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Membrane transporters in drug development and as determinants of precision medicine.Nature reviews. Drug discovery · 2024Review
- Alterations in zonal distribution and plasma membrane localization of hepatocyte bile acid transporters in patients with NAFLD.Hepatology communications · 2024Article
- The Role of CYPs and Transporters in the Biotransformation and Transport of the Anti-hepatitis C Antiviral Agents Asunaprevir, Daclatasvir, and Beclabuvir: Impact of Liver Disease, Race and Drug-drug Interactions on Safety and Efficacy.Current drug metabolism · 2024Review
- Importance of N-Glycosylation for the Expression and Function of Human Organic Anion Transporting Polypeptide 2B1.ACS pharmacology & translational science · 2023Article
- Considerations for Physiologically Based Modeling in Liver Disease: From Nonalcoholic Fatty Liver (NAFL) to Nonalcoholic Steatohepatitis (NASH).Clinical pharmacology and therapeutics · 2023Review
- Investigation on acquired palbociclib resistance by LC-MS based multi-omics analysis.Frontiers in molecular biosciences · 2023Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsN-linked glycosylation of proteins is critical for proper protein folding and trafficking to the plasma membrane. Drug transporters are one class of proteins that have reduced function when glycosylation is impaired. N-linked glycosylation of plasma proteins has also been investigated as a biomarker for several liver diseases, including non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to assess the transcriptomic expression of genes involved in protein processing and glycosylation, and to determine the glycosylation status of key drug transporters during human NAFLD progression.
methodsHuman liver samples diagnosed as healthy, steatosis, and non-alcoholic steatohepatitis (NASH) were analysed for gene expression of glycosylation-related genes and for protein glycosylation using immunoblot.
resultsGenes involved in protein processing in the ER and biosynthesis of N-glycans were significantly enriched for down-regulation in NAFLD progression. Included in the down regulated N-glycan biosynthesis category were genes involved in the oligosaccharyltransferase complex, N-glycan quality control, N-glycan precursor biosynthesis, N-glycan trimming to the core, and N-glycan extension from the core. N-glycan degradation genes were unaltered in the progression to NASH. Immunoblot analysis of the uptake transporters organic anion transporting polypeptide-1B1 (OATP1B1), OATP1B3, OATP2B1, and Sodium/Taurocholate Co-transporting Polypeptide (NTCP) and the efflux transporter multidrug resistance-associated protein 2 (MRP2) demonstrated a significant loss of glycosylation following the progression to NASH.
conclusionsThese data suggest that the loss of glycosylation of key uptake and efflux transporters in humans NASH may influence transporter function and contribute to altered drug disposition observed in NASH.
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Registered trials
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.