{
  "abstract": "Limb-girdle muscular dystrophy R6, formerly LGMD2F, is caused by mutations in the δ-sarcoglycan (Sgcd) gene and is characterized by progressive skeletal muscle degeneration. Although loss of δ-SG protein compromises sarcolemma stability, how δ-sarcoglycan deficiency reshapes inflammatory and metabolic gene programs across distinct skeletal muscles remains incompletely defined. Here, we profiled soleus and extensor digitorum longus (EDL) muscles from wild-type and Sgcd−/− mice treated with vehicle or (-)-epicatechin, a dietary flavanol with anti-inflammatory and antioxidant properties, using bulk RNA sequencing, pathway analysis, immune-cell deconvolution, and RT-qPCR validation. δ-sarcoglycan deficiency produced broad transcriptional remodeling while preserving baseline muscle-type identity. Across soleus and EDL, the dystrophic transcriptome was marked by interferon-associated inflammatory remodeling together with repression of oxidative and mitochondrial metabolic programs. Within this shared disease state, soleus displayed a stronger induced inflammatory component, including innate-sensing and macrophage-linked features. Computational deconvolution, which estimates immune-cell proportions from bulk transcriptomes (quanTIseq and mMCP-counter), supported genotype-dependent shifts in immune-cell signatures, with concordant monocyte/macrophage signals. Finally, (-)-epicatechin produced context-dependent transcriptional effects and attenuated a defined interferon/innate-sensing module in dystrophic soleus, as supported by RNA-seq and RT-qPCR. Together, these findings establish inflammatory remodeling with a prominent interferon component and oxidative metabolic repression as central transcriptional features of δ-sarcoglycan-deficient skeletal muscle, while revealing an amplified innate-sensing and immune-enriched module in dystrophic soleus that remains transcriptionally responsive to (-)-epicatechin treatment.",
  "abstract_shown": true,
  "affiliations": [
    "Laboratorio de Epigenética de la Regeneración Muscular, Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados (CINVESTAV-IPN), Mexico City 07360, Mexico",
    "Laboratorio de Epigenética de la Regeneración Muscular, Centro de Investigación sobre el Envejecimiento, Centro de Investigación y de Estudios Avanzados (CINVESTAV-IPN), Mexico City 14330, Mexico",
    "Laboratorio de Medicina Genómica, Departamento de Genética, Instituto Nacional de Rehabilitación–Luis Guillermo Ibarra Ibarra, Mexico City 14389, Mexico",
    "Subdirección de Enseñanza e Investigación, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Mexico City 03100, Mexico",
    "Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Mexico City 07700, Mexico"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Amairani Cancino-Bello",
      "orcid": "0009-0004-9372-6990"
    },
    {
      "affs": [
        0
      ],
      "name": "Mauricio Hernández-Somilleda"
    },
    {
      "affs": [
        0
      ],
      "name": "Erick Bahena-Culhuac",
      "orcid": "0009-0009-5947-9275"
    },
    {
      "affs": [
        1
      ],
      "name": "Estela G. García-González"
    },
    {
      "affs": [
        2
      ],
      "name": "Oscar Hernández-Hernández",
      "orcid": "0000-0001-6388-2459"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Ramón M. Coral-Vázquez",
      "orcid": "0000-0001-6126-2002"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "J. Manuel Hernández-Hernández",
      "orcid": "0000-0001-7624-9986"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/6repm3j8q67n7.bib",
  "cited_by": 0,
  "doi": "10.3390/biom16101511",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702233/?tool=EBI",
  "id": "6repm3j8q67n7",
  "issns": [
    "2218-273X"
  ],
  "landing_url": "https://www.mdpi.com/2218-273X/16/10/1511",
  "language": "eng",
  "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": [
    [
      "lcc",
      "QR1-502"
    ],
    [
      "openalex",
      "1312|Muscle Physiology and Disorders"
    ]
  ],
  "openalex": "W7222920085",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13702233/pdf/?tool=EBI",
  "pmcid": "PMC13702233",
  "pmid": null,
  "published": "2026-10-01",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/6repm3j8q67n7.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:59Z",
      "native_id": "10.3390/biom16101511",
      "source": "crossref",
      "url": "https://www.mdpi.com/2218-273X/16/10/1511"
    },
    {
      "first_seen": "2026-10-30T12:21:45Z",
      "native_id": "PMC:PMC13702233",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13702233"
    },
    {
      "first_seen": "2026-10-31T14:21:22Z",
      "native_id": "035cfb2eab6047a59df260aa194ea623",
      "source": "doaj",
      "url": "https://doi.org/10.3390/biom16101511"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Muscle Physiology and Disorders",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Interferon-Associated Inflammatory Remodeling and Oxidative Metabolic Repression Define the Skeletal Muscle Transcriptomic Landscape of δ-Sarcoglycan Deficiency",
  "title_text": "Interferon-Associated Inflammatory Remodeling and Oxidative Metabolic Repression Define the Skeletal Muscle Transcriptomic Landscape of δ-Sarcoglycan Deficiency",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T14:21:22Z",
  "url": "https://research.draconitic.com/paper/6repm3j8q67n7",
  "venue": "Biomolecules",
  "versions": []
}