{
  "abstract": "Pathological hypoxia following cutaneous injury is a critical driver of wound chronicity and fibrotic remodeling. The nuclear receptor binding SET domain protein 2 (NSD2)/lysine demethylase 2A (KDM2A)–histone H3 lysine 36 dimethylation (H3K36me2) axis is a known regulator of hypoxia-induced epithelial-to-mesenchymal transition (EMT) in malignancy; however, its role in skin repair remains largely unexplored. We investigated whether poly-L-lactic acid (PLLA) could attenuate fibrotic remodeling by modulating the NSD2/KDM2A–H3K36me2 axis and examining angiogenic signaling. We used a murine 9 mm punch-wound model for in vivo assessment and HaCaT keratinocytes and human dermal fibroblasts (HDFs) exposed to 2% O2 as in vitro hypoxia models. PLLA was administered to evaluate its impact on angiogenic signaling, collagen architecture, and the NSD2/KDM2A pathway. PLLA was associated with increased angiogenic markers and reduced expression of several hypoxia-associated epigenetic and fibrotic markers. In mice, PLLA increased vascular endothelial growth factor (VEGF)/VEGF receptor 2 expression and blood vessel abundance. In addition, PLLA decreased NSD2 and H3K36me2 levels while increasing KDM2A levels. Histological analysis showed less dense collagen staining and a change in the collagen type I/type III staining ratio, alongside a smaller photographically defined residual lesion area. Under controlled hypoxic conditions in vitro, PLLA suppressed EMT-related transcription factors, including Snail, Slug, and Twist, in keratinocytes and attenuated transforming growth factor-β1/phosphorylated mothers against decapentaplegic homolog 2/3 signaling and α-smooth muscle actin expression in fibroblasts. These findings support further study of PLLA-associated changes in vascular, epithelial, and fibrotic markers during wound remodeling.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Anatomy & Cell Biology, College of Medicine, Gachon University, Incheon 21936, Republic of Korea",
    "Functional Cellular Networks Laboratory, Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Republic of Korea",
    "LIBON Inc., Incheon 22006, Republic of Korea",
    "Maylin Apgujeong Clinic, Seoul 06024, Republic of Korea",
    "Maylin Clinic Jamsil Lotte Hotel Branch, Seoul 05554, Republic of Korea",
    "Director Global Clinic Gangnam, Seoul 06611, Republic of Korea",
    "Department of Thoracic and Cardiovascular Surgery, Gachon University Gil Medical Center, Gachon University, Incheon 21565, Republic of Korea",
    "Department of Health Sciences and Technology, Gachon Advanced Institute for Health & Sciences and Technology (GAIHST), Gachon University, Incheon 21999, Republic of Korea"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Kyung-A Byun",
      "orcid": "0000-0001-7486-9137"
    },
    {
      "affs": [
        0,
        1,
        3
      ],
      "name": "Hyoung Moon Kim",
      "orcid": "0000-0001-9068-5813"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Seyeon Oh"
    },
    {
      "affs": [
        0,
        1,
        4
      ],
      "name": "Ki Woong Yu"
    },
    {
      "affs": [
        5
      ],
      "name": "Ji Min Lee"
    },
    {
      "affs": [
        6
      ],
      "name": "Kuk Hui Son",
      "orcid": "0000-0002-0595-5645"
    },
    {
      "affs": [
        0,
        2,
        7
      ],
      "name": "Kyunghee Byun",
      "orcid": "0000-0001-8678-8932"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bxb3nqhhepg8w.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27198874",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665362/?tool=EBI",
  "id": "bxb3nqhhepg8w",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13665362",
  "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",
      "2742|Wound Healing and Treatments"
    ]
  ],
  "openalex": "W7220372992",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665362/pdf/?tool=EBI",
  "pmcid": "PMC13665362",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/bxb3nqhhepg8w.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:35Z",
      "native_id": "PMC:PMC13665362",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13665362"
    },
    {
      "first_seen": "2026-10-30T12:18:55Z",
      "native_id": "10.3390/ijms27198874",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/19/8874"
    }
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2742|Wound Healing and Treatments",
      "subfield": "general"
    }
  ],
  "title": "Poly-L-Lactic Acid Attenuates Fibrotic Remodeling During Cutaneous Wound Healing",
  "title_text": "Poly-L-Lactic Acid Attenuates Fibrotic Remodeling During Cutaneous Wound Healing",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:55Z",
  "url": "https://research.draconitic.com/paper/bxb3nqhhepg8w",
  "venue": "International journal of molecular sciences",
  "versions": []
}