{
  "abstract": "Inadequate autophagy promotes smoking-induced cellular senescence involved in chronic obstructive pulmonary disease (COPD) pathogenesis. Transcription factor EB (TFEB) is a master regulator of the autophagy-lysosome axis. For the first time, we investigated the therapeutic potential of pemafibrate, a putative TFEB inducer. COPD lung epithelial cells showed reduced TFEB expression. Pemafibrate enhanced autophagy/mitophagy flux and restored lysosomal acidification observed during cigarette smoke (CS) extract exposure in human bronchial epithelial cells, resulting in reduced cellular senescence. TFEB knockdown demonstrated involvement of pemafibrate-induced TFEB in these effects. Pemafibrate induced TFEB expression, mitigated alveolar enlargement and airflow obstruction, and attenuated the CS-induced increase in static lung compliance in a long-term CS-exposed mouse model. It reduced the CS exposure-induced cellular senescence, possibly through autophagy/mitophagy, as suggested by bulk RNA sequencing of mouse lungs. A retrospective cohort study showed that patients given pemafibrate displayed attenuated FEV1.0 decline compared with those given bezafibrate or fenofibrate. In conclusion, pemafibrate is a promising therapeutic agent for COPD, potentially exerting its effects through the regulation of the TFEB-autophagy/mitophagy-lysosome axis.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Respiratory Diseases, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 19,
  "authors": [
    {
      "name": "S. Matsubayashi"
    },
    {
      "affs": [
        0
      ],
      "name": "S. Ito"
    },
    {
      "name": "Y. Hosaka"
    },
    {
      "name": "M. Yoshida"
    },
    {
      "name": "T. Kadota"
    },
    {
      "name": "M. Hashimoto"
    },
    {
      "name": "S. Hatano"
    },
    {
      "name": "T. Maruyama"
    },
    {
      "name": "S. Fujimoto"
    },
    {
      "name": "S. Nishioka"
    },
    {
      "name": "S. Inukai"
    },
    {
      "name": "Y. Fujita"
    },
    {
      "name": "S. Minagawa"
    },
    {
      "name": "H. Hara"
    },
    {
      "name": "T. Nakada"
    },
    {
      "name": "K. Nakayama"
    },
    {
      "name": "T. Ohtuska"
    },
    {
      "name": "K. Kuwano"
    },
    {
      "name": "J. Araya"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7esdt7zcyv2bg.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.31.26361865",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.08.31.26361865v1.full",
  "id": "7esdt7zcyv2bg",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.08.31.26361865v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "respiratory medicine"
    ],
    [
      "openalex",
      "2713|Autophagy in Disease and Therapy"
    ]
  ],
  "openalex": "W7206175014",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.08.31.26361865v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-31",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/7esdt7zcyv2bg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:35Z",
      "native_id": "10.64898/2026.08.31.26361865",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.08.31.26361865v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2713|Autophagy in Disease and Therapy",
      "subfield": "epidemiology-public-health"
    }
  ],
  "title": "Senotherapeutic role of pemafibrate through autophagy/mitophagy regulation in chronic obstructive pulmonary disease",
  "title_text": "Senotherapeutic role of pemafibrate through autophagy/mitophagy regulation in chronic obstructive pulmonary disease",
  "type": "preprint",
  "updated_at": "2026-10-30T12:17:35Z",
  "url": "https://research.draconitic.com/paper/7esdt7zcyv2bg",
  "venue": "medRxiv",
  "versions": []
}