Aline Guerci, Sotiropoulos Athanassia
Bioarchitecture. 2012 May 1;2(3):88-90. doi: 10.4161/bioa.20699.
Adult skeletal muscles adapt their fiber size to workload. We show that serum response factor (Srf) is required for satellite cell-mediated hypertrophic muscle growth. Deletion of Srf from myofibers, and not satellite cells, blunts overload-induced hypertrophy, and impairs satellite cell proliferation and recruitment to pre-existing fibers. We reveal a gene network in which Srf within myofibers modulates interleukin-6 and cyclooxygenase-2/interleukin-4 expressions and therefore exerts a paracrine control of satellite cell functions. In Srf-deleted muscles, in vivo overexpression of interleukin-6 is sufficient to restore satellite cell proliferation, but not satellite cell fusion and overall growth. In contrast, cyclooxygenase-2/interleukin-4 overexpression rescues satellite cell recruitment and muscle growth without affecting satellite cell proliferation, identifying altered fusion as the limiting cellular event. These findings unravel a role for Srf in the translation of mechanical cues applied to myofibers into paracrine signals, which in turn will modulate satellite cell functions and support muscle growth.
成年骨骼肌会根据工作负荷调整其纤维大小。我们发现，血清反应因子（Srf）是卫星细胞介导的肌肉肥大生长所必需的。从肌纤维而非卫星细胞中删除Srf会减弱超负荷诱导的肥大，并损害卫星细胞的增殖以及其向已有纤维的募集。我们揭示了一个基因网络，其中肌纤维内的Srf调节白细胞介素-6和环氧合酶-2/白细胞介素-4的表达，从而对卫星细胞功能进行旁分泌控制。在缺失Srf的肌肉中，体内白细胞介素-6的过表达足以恢复卫星细胞的增殖，但不能恢复卫星细胞的融合和整体生长。相比之下，环氧合酶-2/白细胞介素-4的过表达可挽救卫星细胞的募集和肌肉生长，而不影响卫星细胞的增殖，这表明融合改变是限制细胞活动的因素。这些发现揭示了Srf在将施加于肌纤维的机械信号转化为旁分泌信号中的作用，进而调节卫星细胞功能并支持肌肉生长。
