ArticleJournal of hepatology2018
hiPSC hepatocyte model demonstrates the role of unfolded protein response and inflammatory networks in α
Article in Journal of hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Meta-Analysis: Redefining Liver Disease Risk in Heterozygous Alpha-1 Antitrypsin Deficiency.Alimentary pharmacology & therapeutics · 2026Pooled it
- Derivation of elephant induced pluripotent stem cells.Nature methods · 2026Article
- Z variant heterozygosity in alpha-1 antitrypsin deficiency: disease risk and treatment implications.Orphanet journal of rare diseases · 2026Article
- AT2-intrinsic Z-AAT expression drives conserved inflammatory and proteotoxic stress responses and predisposes to emphysema.bioRxiv : the preprint server for biology · 2026Article
- Dietary Melegueta pepper alleviates heat stress-induced disruptions in haematobiochemical parameters, liver histopathology and growth performance indices of broiler chickens in tropical conditions.Tropical animal health and production · 2026Article
- Innovative models to explore hepatic involvement in Prader-Willi syndrome.Frontiers in endocrinology · 2026Review
- Rare liver diseases - Etiology, diagnosis and management: A review.Biomolecules & biomedicine · 2025Review
- Application of Induced Pluripotent Stem Cells (iPSCs) in Hereditary and Viral Diseases of the Liver: Modeling and Treatment.International journal of molecular sciences · 2025Review
- Rationale and Design of the Alpha-1 Biomarkers Consortium Study.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2025Article
- Altered polyadenylation site usage in SERPINA1 3'UTR in response to cellular stress affects A1AT protein expression.Scientific reports · 2025Article
- Article
- Liver Disease and Prevalence of Liver Transplantation in Adults With ZZ Alpha-1 Antitrypsin Deficiency-A Meta-Analysis.Liver international communications · 2025Article
- Selection for somatic escape variants in SERPINA1 in the liver of patients with alpha-1 antitrypsin deficiency.Nature genetics · 2025Article
- Indole compounds from fermented soybean products activate the aryl hydrocarbon receptor to reduce liver injury.NPJ science of food · 2025Article
- Spatial covariance reveals isothiocyanate natural products adjust redox stress to restore function in alpha-1-antitrypsin deficiency.Cell reports. Medicine · 2025Article
- A robust reprogramming strategy for generating hepatocyte-like cells usable in pharmaco-toxicological studies.Stem cell research & therapy · 2023Article
- Association of Alpha-1 Antitrypsin Pi*Z Allele Frequency and Progressive Liver Fibrosis in Two Chronic Hepatitis C Cohorts.Journal of clinical medicine · 2022Article
- Human iPSC-hepatocyte modeling of alpha-1 antitrypsin heterozygosity reveals metabolic dysregulation and cellular heterogeneity.Cell reports · 2022Article
- The unfolded protein response to PI*Z alpha-1 antitrypsin in human hepatocellular and murine models.Hepatology communications · 2022Article
- Article
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsα
methodsHuman-induced pluripotent stem cell (hiPSC)-derived hepatocytes provide a novel approach to interrogate the molecular mechanisms of A1ATD because of their patient-specific genetic architecture and reflection of human physiology. To that end, we utilised patient-specific hiPSC hepatocyte-like cells (ZZ-HLCs) derived from an A1ATD (ZZ) patient, which faithfully recapitulated key aspects of the disease at the molecular and cellular level. Subsequent functional and "omics" comparisons of these cells with their genetically corrected isogenic-line (RR-HLCs) and primary hepatocytes/human tissue enabled identification of new molecular markers and disease signatures.
resultsOur studies showed that abnormal A1AT polymer processing (immobilised ER components, reduced luminal protein mobility and disrupted ER cisternae) occurred heterogeneously within hepatocyte populations and was associated with disrupted mitochondrial structure, presence of the oncogenic protein AKR1B10 and two upregulated molecular clusters centred on members of inflammatory (IL-18 and Caspase-4) and unfolded protein response (Calnexin and Calreticulin) pathways. These results were validated in a second patient-specific hiPSC line.
conclusionsOur data identified novel pathways that potentially link the expression of Z A1AT polymers to liver disease. These findings could help pave the way towards identification of new therapeutic targets for the treatment of A1ATD. LAY SUMMARY: This study compared the gene expression and protein profiles of healthy liver cells and those affected by the inherited disease α
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