Lack of PKCθ Promotes Regenerative Ability of Muscle Stem Cells in Chronic Muscle Injury

Piera Filomena Fiore, Anna Benedetti, Martina Sandonà, Luca Madaro, Marco De Bardi, Valentina Saccone, Pier Lorenzo Puri, Cesare Gargioli, Biliana Lozanoska-Ochser, Marina Bouché

Research output: Contribution to journalArticle

Abstract

Duchenne muscular dystrophy (DMD) is a genetic disease characterized by muscle wasting and chronic inflammation, leading to impaired satellite cells (SCs) function and exhaustion of their regenerative capacity. We previously showed that lack of PKCθ in mdx mice, a mouse model of DMD, reduces muscle wasting and inflammation, and improves muscle regeneration and performance at early stages of the disease. In this study, we show that muscle regeneration is boosted, and fibrosis reduced in mdxθ-/- mice, even at advanced stages of the disease. This phenotype was associated with a higher number of Pax7 positive cells in mdxθ-/- muscle compared with mdx muscle, during the progression of the disease. Moreover, the expression level of Pax7 and Notch1, the pivotal regulators of SCs self-renewal, were upregulated in SCs isolated from mdxθ-/- muscle compared with mdx derived SCs. Likewise, the expression of the Notch ligands Delta1 and Jagged1 was higher in mdxθ-/- muscle compared with mdx. The expression level of Delta1 and Jagged1 was also higher in PKCθ-/- muscle compared with WT muscle following acute injury. In addition, lack of PKCθ prolonged the survival and sustained the differentiation of transplanted myogenic progenitors. Overall, our results suggest that lack of PKCθ promotes muscle repair in dystrophic mice, supporting stem cells survival and maintenance through increased Delta-Notch signaling.

Original languageEnglish
JournalInternational Journal of Molecular Sciences
Volume21
Issue number3
DOIs
Publication statusPublished - Jan 31 2020

Keywords

  • Duchenne Muscular Dystrophy
  • mdx
  • muscle satellite cells
  • Protein Kinase C θ

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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