{
  "abstract": "BACKGROUND AND OBJECTIVE: Hepatocyte growth factor receptor (MET) is the key driver of liver regeneration following partial hepatectomy (PHx) but remains poorly understood in the context of acetaminophen-induced liver injury (AILI). In our prior work, hepatocyte-specific MET-knockout mice exhibited severe early injury and high mortality following APAP overdose, limiting the evaluation of MET's direct role in liver regeneration. Given the critical need to identify therapeutic targets that promote recovery during the late stages of AILI, the present study investigates the reparative role of MET using a pharmacological MET inhibitor, capmatinib. METHODS: C57BL/6 J mice (n = 5) received moderate (300 mg/kg) or severe (500 mg/kg) overdose of APAP, followed by capmatinib (15 mg/kg) or vehicle. Liver injury and regeneration parameters were assessed using histology, immunoblotting, and immunohistochemistry. RESULTS: Vehicle and capmatinib-treated mice showed comparable peak injury under both moderate and severe APAP overdose settings, enabling a direct assessment of regeneration independent of initial injury severity. During the recovery phase, capmatinib-treated mice displayed significant impairment in resolution of injury (p < 0.05), indicated by sustained centrilobular necrosis, especially after severe APAP overdose. While MET inhibition delayed and dampened hepatocyte proliferation response following moderate APAP overdose, it severely impaired hepatocyte proliferation following the higher APAP overdose. Impaired liver regeneration upon MET inhibition was associated with marked reduction in ERK signaling and downstream expression of core cell cycle protein, cyclin-D1. CONCLUSIONS: Overall, MET inhibition using capmatinib notably impaired regeneration and resolution of AILI, without altering peak injury, emphasizing MET's direct role in reparative response.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.",
    "Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Siddhi Jain"
    },
    {
      "affs": [
        0
      ],
      "name": "Ranjan Mukherjee"
    },
    {
      "affs": [
        0
      ],
      "name": "Gillian Williams"
    },
    {
      "affs": [
        0
      ],
      "name": "Anne Orr"
    },
    {
      "affs": [
        0
      ],
      "name": "Saidikrom Mardiev"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "George K Michalopoulos"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Bharat Bhushan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9tmxwd45dxkc9.bib",
  "cited_by": 0,
  "doi": "10.1016/j.taap.2026.118079",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13729905/",
  "id": "9tmxwd45dxkc9",
  "issns": [
    "0041-008X",
    "1096-0333"
  ],
  "landing_url": "https://doi.org/10.1016/j.taap.2026.118079",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "3004|Drug-Induced Hepatotoxicity and Protection"
    ]
  ],
  "openalex": "W7221182506",
  "pdf_url": "https://www.sciencedirect.com/science/article/pii/S0041008X26003753/pdf",
  "pmcid": "PMC13729905",
  "pmid": "42854925",
  "published": "2026-10-09",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9tmxwd45dxkc9.ris",
  "sources": [
    {
      "first_seen": "2026-11-07T12:22:38Z",
      "native_id": "PMC13729905",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.taap.2026.118079"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:3004|Drug-Induced Hepatotoxicity and Protection",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Pharmacological inhibition of MET impairs hepatic regeneration and recovery in a murine model of acetaminophen-induced liver injury",
  "title_text": "Pharmacological inhibition of MET impairs hepatic regeneration and recovery in a murine model of acetaminophen-induced liver injury",
  "type": "peer-reviewed",
  "updated_at": "2026-11-07T12:22:38Z",
  "url": "https://research.draconitic.com/paper/9tmxwd45dxkc9",
  "venue": "Toxicology and applied pharmacology",
  "versions": []
}