Erschienen:
[Erscheinungsort nicht ermittelbar]: [Verlag nicht ermittelbar], 2020
Sprache:
Englisch
Identifikator:
Entstehung:
Hochschulschrift:
Dissertation, 2020
Anmerkungen:
Beschreibung:
Skeletal muscle regeneration following injury depends on the ability of satellite cells (SCs) to proliferate, differentiate, self- renew, and eventually repair the damage. SC function declines with age and in certain pathological conditions, such as Duchenne Muscular Dystrophy (DMD). Previously we demonstrated that lack or inhibition of Protein kinase Cθ (PKCθ), in a mouse model of DMD (mdx mouse) is associated with a significant improvement in muscle regeneration, which is primarly due to reduced inflammation; hovever, it might also depend on a direct effect on SCs. Therefore, in this study we examined the potential role of PKCθ in SC function. We show that PKCθ is expressed in SCs and its active form is localized to the chromosomes during prophase, to the centrosomes during metaphase and to the midbody during cytokinesis. Interestingly, symmetric division of Pax7+/MyoD- SCs and the number of self-renewing SCs were significantly increased on single myofibers isolated from PKCθ-/- mice compared to wild type, after 2 and 3 days in culture. Genetic ablation of PKCθ or its pharmacological inhibition in vivo had no effect on SC number in healthy muscle. By contrast, after induction of muscle injury lack or inhibition of PKCθ resulted in a significant expansion of a population of self-renewing SCs known to contribute to the maintenance of the satellite cell pool. Lack of PKCθ had no effect on SC proliferation in vitro and in vivo and did not alter the inflammatory milieu after acute injury in muscle. Thus, the enhanced self-renewal ability of SCs in PKCθ-/- mice is not due to an increased proliferation or a different crosstalk between SCs and immune cells. Together, these results suggest that PKCθ absence or inhibition lead to an increased SC self-renewal by stimulating their expansion through symmetric division. In conclusion, PKCθ may be a promising target to manipulate satellite cell self-renewal in pathological conditions.