{
  "abstract": "Background\n\nThe severe phenotype of alpha-1-antitrypsin deficiency (AATD) is typically caused by the Z-mutation within the SERPINA1 gene. The Glu342Lys substitution causes misfolding and polymerisation of the alpha-1-antitrypsin (AAT) protein and its accumulation in the ER. This increases the susceptibility of hepatocytes towards ER-stress.Methods\n\nHere, we present an induced pluripotent stem cell (iPSC)-based hepatic model to study AATD. We tested 4 distinct compounds on our cells that have been reported to reduce ZAAT polymers in hepatocytes. We quantified their effect via immunocytochemistry and performed next generation sequencing for the most effective compounds: Carbamazepine (CBZ) and Suberoylanilide hydroxamic acid (SAHA).Results\n\nWe demonstrate that iPSCs from AATD patients differentiate equally well to hepatocyte-like cells (HLCs) as control iPSCs. We detected ZAAT polymers in patient-derived HLCs which could be reduced by SAHA or CBZ treatment. Transcriptome analyses revealed major differences in metabolism and signalling between control and AATD HLCs and indicated increased stress levels affecting intracellular organelles. Importantly, the transcriptomes of control and patient-derived cells separated into distinct clusters with respect to the expression of Heat-shock protein (HSP) encoding genes.Conclusion\n\nSAHA treatment increased expression of various HSPs which might contribute towards reduced ZAAT polymers.",
  "abstract_shown": true,
  "affiliations": [
    "Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University, Moorenstraße 5, 40225, Düsseldorf, Germany.",
    "Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen, Germany.",
    "Department of Gastroenterology and Hepatology, Medical University Lausitz - Carl Thiem (MUL-CT), Cottbus, Germany.",
    "Institute for Stem Cell Research and Regenerative Medicine, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University, Moorenstraße 5, 40225, Düsseldorf, Germany. james.adjaye@med.uni-duesseldorf.de.",
    "Faculty of Life Sciences & Medicine, Department of Inflammation Biology, King's College London, Guy's Campus, Great Maze Pond, London, SE1 1UL, UK. james.adjaye@med.uni-duesseldorf.de."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Nina Graffmann"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Rabea Hokamp"
    },
    {
      "affs": [
        0
      ],
      "name": "Christiane Lörch"
    },
    {
      "affs": [
        1
      ],
      "name": "Malin Fromme"
    },
    {
      "affs": [
        0
      ],
      "name": "Wasco Wruck"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Pavel Strnad"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "James Adjaye"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6tm7z94ya6rfk.bib",
  "cited_by": 0,
  "doi": "10.1186/s13287-026-05365-y",
  "fulltext_url": "https://europepmc.org/articles/PMC13718072",
  "id": "6tm7z94ya6rfk",
  "issns": [
    "1757-6512"
  ],
  "landing_url": "https://europepmc.org/article/MED/42958433",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "1307|Endoplasmic Reticulum Stress and Disease"
    ]
  ],
  "openalex": "W7223967378",
  "pdf_url": "https://europepmc.org/articles/PMC13718072?pdf=render",
  "pmcid": "PMC13718072",
  "pmid": "42958433",
  "published": "2026-10-27",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/6tm7z94ya6rfk.ris",
  "sources": [
    {
      "first_seen": "2026-11-01T00:20:36Z",
      "native_id": "MED:42958433",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42958433"
    },
    {
      "first_seen": "2026-11-02T12:22:13Z",
      "native_id": "PMC13718072",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s13287-026-05365-y"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:1307|Endoplasmic Reticulum Stress and Disease",
      "subfield": "cell-biology"
    }
  ],
  "title": "SAHA increases chaperone expression and reduces Z-alpha-1-antitrypsin polymers in a patient specific iPSC-based liver model for alpha-1-antitrypsin deficiency.",
  "title_text": "SAHA increases chaperone expression and reduces Z-alpha-1-antitrypsin polymers in a patient specific iPSC-based liver model for alpha-1-antitrypsin deficiency.",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:22:13Z",
  "url": "https://research.draconitic.com/paper/6tm7z94ya6rfk",
  "venue": "Stem cell research & therapy",
  "versions": []
}