Dept AHFMO, University of Rome "La Sapienza", Via A. Scarpa 14, 00161 Rome, Italy.
Int J Mol Sci. 2020 Mar 31;21(7):2419. doi: 10.3390/ijms21072419.
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.
损伤后骨骼肌的再生依赖于卫星细胞 (SCs) 的增殖、自我更新和最终分化能力。调节自我更新过程的因素知之甚少。在这项研究中，我们研究了 PKCθ 在 SC 自我更新和分化中的作用。我们表明 PKCθ 在 SCs 中表达，其活性形式在有丝分裂期间定位于染色体、中心体和中期。缺乏 PKCθ 通过调节 Pard3 极性蛋白定位促进 SC 对称自我更新分裂，而不影响整体增殖率。体内敲除 PKCθ 或其药理学抑制均不影响健康肌肉中的 SC 数量。相比之下，在诱导肌肉损伤后，缺乏或抑制 PKCθ 会导致静止 SC 池显著扩张。最后，我们表明缺乏 PKCθ 不会改变肌肉急性损伤后的炎症环境，这表明 PKCθ-/- 小鼠中 SC 自我更新能力的增强不是由于炎症环境的改变。总之，这些结果表明 PKCθ 通过刺激其通过对称分裂进行扩张，在 SC 自我更新中发挥重要作用，它可能代表一种有前途的靶点，可在病理条件下操纵卫星细胞自我更新。
