Targeting pkcθ promotes satellite cell self-renewal

Anna Benedetti, Piera Filomena Fiore, Luca Madaro, Biliana Lozanoska-Ochser, Marina Bouché

Research output: Contribution to journalArticlepeer-review

Abstract

Skeletal muscle regeneration following injury depends on the ability of satellite cells (SCs) to proliferate, self-renew, and eventually differentiate. The factors that regulate the process of self-renewal are poorly understood. In this study we examined the role of PKCθ in SC self-renewal and differentiation. We show that PKCθ is expressed in SCs, and its active form is localized to the chromosomes, centrosomes, and midbody during mitosis. Lack of PKCθ promotes SC symmetric self-renewal division by regulating Pard3 polarity protein localization, without affecting the overall proliferation rate. Genetic ablation of PKCθ or its pharmacological inhibition in vivo did not affect SC number in healthy muscle. By contrast, after induction of muscle injury, lack or inhibition of PKCθ resulted in a significant expansion of the quiescent SC pool. Finally, we show that lack of PKCθ does not alter the inflammatory milieu after acute injury in muscle, suggesting that the enhanced self-renewal ability of SCs in PKCθ-/-mice is not due to an alteration in the inflammatory milieu. Together, these results suggest that PKCθ plays an important role in SC self-renewal by stimulating their expansion through symmetric division, and it may represent a promising target to manipulate satellite cell self-renewal in pathological conditions.

Original languageEnglish
Article number2419
JournalInternational Journal of Molecular Sciences
Volume21
Issue number7
DOIs
Publication statusPublished - Apr 1 2020

Keywords

  • Muscle regeneration
  • Protein kinase C θ
  • Satellite cells
  • Self-renewal

ASJC Scopus subject areas

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

Fingerprint

Dive into the research topics of 'Targeting pkcθ promotes satellite cell self-renewal'. Together they form a unique fingerprint.

Cite this