{
  "abstract": "Liver fibrosis, characterized by excessive accumulation of the extracellular matrix (ECM), is caused by an imbalance between fibrogenesis and fibrolysis. Effective antifibrotic therapy requires the regulation of hepatic stellate cells (HSCs) through the production of collagen and matrix metalloproteinases (MMPs). The TGF-β/Smad and Wnt/β-catenin pathways play central roles in this regulation. In this study, we investigated whether IC-2, a Wnt/β-catenin inhibitor derived from ICG-001, reduces TGF-β/Smad and Wnt/β-catenin signaling in HSCs in vitro. We further examined the anti-fibrotic effects in two fibrosis models: carbon tetrachloride (CCl4)-treated mice and high-fat diet (HFD)-fed ob/ob mice. IC-2 markedly suppressed the TGF-β/Smad and Wnt/β-catenin pathway in HSCs. Furthermore, IC-2 markedly ameliorated liver fibrosis in CCl4-treated mice, accompanied with suppressed HSC activation and enhanced collagenolytic activity. IC-2 also attenuated fibrosis in the livers of HFD-fed mice. Co-immunoprecipitation analysis confirmed that IC-2 disrupts the β-catenin/CREB-binding protein (CBP) complex. IC-2 specifically induced MMP-1 expression in human HSCs, while the JNK inhibitor SP600125 suppressed IC-2-mediated MMP-1 induction at 48 h, but not at 24 h. It is suggested that this delayed effect may be due to a delayed transcriptional response or indirect signaling cascade downstream of JNK activation. These findings demonstrate that IC-2 mitigates liver fibrosis by inhibiting HSC activation and promoting collagenolysis, highlighting its therapeutic potential in cirrhosis.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Regenerative Medicine and Therapeutics, Department of Genomic Medicine and Regenerative Therapy, School of Medicine, Faculty of Medicine, Tottori University, Yonago 683-8503, Tottori, Japan",
    "KanonCure Inc., Yonago 683-8503, Tottori, Japan",
    "Research Initiative Center, Tottori University, Tottori 680-8550, Tottori, Japan"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Noriko Itaba",
      "orcid": "0000-0002-6866-1986"
    },
    {
      "affs": [
        0
      ],
      "name": "Ken-ichiro Abe",
      "orcid": "0000-0002-7664-7404"
    },
    {
      "affs": [
        0
      ],
      "name": "Yohei Kono",
      "orcid": "0000-0001-8264-9417"
    },
    {
      "affs": [
        0
      ],
      "name": "Hiroki Shimizu"
    },
    {
      "affs": [
        2
      ],
      "name": "Hiroyuki Oka"
    },
    {
      "affs": [
        2
      ],
      "name": "Minoru Morimoto"
    },
    {
      "affs": [
        0
      ],
      "name": "Daisuke Nanba",
      "orcid": "0000-0002-9765-9113"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Goshi Shiota",
      "orcid": "0000-0001-9756-8791"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/94wec5p6pw4bq.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219522",
  "fulltext_url": null,
  "id": "94wec5p6pw4bq",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9522",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2721|Liver physiology and pathology"
    ]
  ],
  "openalex": "W7223907872",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-24",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/94wec5p6pw4bq.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:57Z",
      "native_id": "10.3390/ijms27219522",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9522"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2721|Liver physiology and pathology",
      "subfield": "general"
    }
  ],
  "title": "Therapeutic Targeting of Hepatic Stellate Cell Inactivation and Collagen Degradation by IC-2 Mitigates Liver Fibrosis",
  "title_text": "Therapeutic Targeting of Hepatic Stellate Cell Inactivation and Collagen Degradation by IC-2 Mitigates Liver Fibrosis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:57Z",
  "url": "https://research.draconitic.com/paper/94wec5p6pw4bq",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}