{
  "abstract": "Liver fibrosis results from excessive extracellular matrix (ECM) deposition following chronic hepatocyte injury. Hepatic stellate cell (HSC) activation is central to fibrogenesis; however, the regulatory mechanisms controlling this process remain unclear. Protein acetylation, regulated by histone acetyltransferases and deacetylases (HDACs), modulates gene expression and protein stability. To date, no studies have explored acetylation dynamics during HSC activation using proteomic approaches. In this study, we investigated the role of acetylation in HSC activation and liver fibrosis. Proteomic profiling of primary mouse HSCs was performed to assess global protein acetylation and the expression of HDACs and SIRTs during HSC activation. Activated HSCs exhibited reduced global protein acetylation, increased HDAC2/3/6 expression, and decreased SIRTs expression. Selective inhibition of HDAC6, but not HDAC2/3, suppressed TGF-β-induced HSC activation. TGF-β increased HDAC6 expression via Smad3-dependent transcription, and HDAC6 promoted fibrogenic gene expression through Smad activation. Proteomic screening identified acetyl-CoA acetyltransferase 1 (ACAT1) as a novel HDAC6 substrate; HDAC6 overexpression enhanced ACAT1 binding and reduced its acetylation. In vivo, pharmacological inhibition of HDAC6 lowered ALT and AST levels and improved histological changes in fibrotic mice. Our results suggest that selective HDAC6 inhibition may represent a promising therapeutic strategy for treating liver fibrosis.",
  "abstract_shown": true,
  "affiliations": [
    "MRC-OSTRC, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Chosun University, Gwangju, 61452, Republic of Korea.",
    "KNU G-LAMP Project Group, KNU Institute of Basic Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.",
    "Honam Regional Future Drug Development Convergence Education & Research Division (BK21 FOUR), Chosun University, Republic of Korea.",
    "College of Korean Medicine, Dongshin University, Naju, Jeollanam-do, 58245, South Korea.",
    "Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon, Korea.",
    "School of Pharmacy, Jeonbuk National University, Jeonju, 54896, Republic of Korea.",
    "Department of Anatomy and Convergence Medical Science, College of Medicine, Institute of Health Sciences, Gyeongsang National University, Jinju 52727, Republic of Korea.",
    "Central Research Center, Okchundang Inc., Daegu 41059, Republic of Korea.",
    "School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Ji Hyun Lee"
    },
    {
      "affs": [
        1
      ],
      "name": "Ann-Yae Na"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Ji Hye Kim"
    },
    {
      "affs": [
        0
      ],
      "name": "Tae Hyun Park"
    },
    {
      "affs": [
        3
      ],
      "name": "Ji Hye Yang"
    },
    {
      "affs": [
        4
      ],
      "name": "Joo Yong Lee"
    },
    {
      "affs": [
        5
      ],
      "name": "Chang Yeob Han"
    },
    {
      "affs": [
        6
      ],
      "name": "Sohi Kang"
    },
    {
      "affs": [
        7
      ],
      "name": "Il Je Cho"
    },
    {
      "affs": [
        8
      ],
      "name": "Sangkyu Lee"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Sung Hwan Ki"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/c24xsqwk13n5c.bib",
  "cited_by": 0,
  "doi": "10.7150/ijbs.137447",
  "fulltext_url": "https://europepmc.org/articles/PMC13685615",
  "id": "c24xsqwk13n5c",
  "issns": [
    "1449-2288"
  ],
  "landing_url": "https://europepmc.org/article/MED/42910219",
  "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": [
    [
      "openalex",
      "2721|Liver physiology and pathology"
    ]
  ],
  "openalex": "W7214680319",
  "pdf_url": "https://europepmc.org/articles/PMC13685615?pdf=render",
  "pmcid": "PMC13685615",
  "pmid": "42910219",
  "published": "2026-09-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/c24xsqwk13n5c.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:14Z",
      "native_id": "MED:42910219",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42910219"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2721|Liver physiology and pathology",
      "subfield": "general"
    }
  ],
  "title": "Histone acetyltransferases and deacetylase 6 (HDAC6) Promotes Hepatic Stellate Cell Activation and Liver Fibrosis.",
  "title_text": "Histone acetyltransferases and deacetylase 6 (HDAC6) Promotes Hepatic Stellate Cell Activation and Liver Fibrosis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:14Z",
  "url": "https://research.draconitic.com/paper/c24xsqwk13n5c",
  "venue": "International journal of biological sciences",
  "versions": []
}