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<p>CD146 + interstitial cells are myogenic progenitors which contribute to skeletal muscle regeneration. However, their role in Duchenne muscular dystrophy (DMD) remains unclear. We compared CD146 + cells from wild-type and mdx mice, revealing distinct molecular and functional differences. <i>Mdx</i> CD146 + differentiated less efficiently into myoblasts and multinucleated myotubes but more efficiently into fibroblasts and adipocytes <i>in vitro</i>. Conditioned medium from <i>mdx</i> CD146 + cells impaired endothelial cell differentiation, through dysregulation of Sdf-1 and Angpt2 secretion. Transcriptomic analyses further reveal a dysregulation of key muscle-related and pro-angiogenic genes, along with an upregulation of fibrosis-associated factors. Mechanistically, we identify changes in the NF-κB, c-Jun, and c-Fos pathways activity as contributors to these pathological changes. These findings suggest that CD146 + cells may play a previously unrecognized role in promoting muscle fibrosis and vascular dysfunction in DMD, rather than aiding regeneration as observed in wild-type.</p>

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CD146 + interstitial cells contribute to the dystrophic skeletal muscle phenotype in vitro

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月24日

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  • Bartosz Mierzejewski,
  • Zuzanna Michalska,
  • Dominika Kulma,
  • Aleksandra Bos,
  • Wladyslawa Streminska,
  • Zbigniew Bartoszewicz,
  • Edyta Brzoska

摘要

CD146 + interstitial cells are myogenic progenitors which contribute to skeletal muscle regeneration. However, their role in Duchenne muscular dystrophy (DMD) remains unclear. We compared CD146 + cells from wild-type and mdx mice, revealing distinct molecular and functional differences. Mdx CD146 + differentiated less efficiently into myoblasts and multinucleated myotubes but more efficiently into fibroblasts and adipocytes in vitro. Conditioned medium from mdx CD146 + cells impaired endothelial cell differentiation, through dysregulation of Sdf-1 and Angpt2 secretion. Transcriptomic analyses further reveal a dysregulation of key muscle-related and pro-angiogenic genes, along with an upregulation of fibrosis-associated factors. Mechanistically, we identify changes in the NF-κB, c-Jun, and c-Fos pathways activity as contributors to these pathological changes. These findings suggest that CD146 + cells may play a previously unrecognized role in promoting muscle fibrosis and vascular dysfunction in DMD, rather than aiding regeneration as observed in wild-type.