McKay Bryon R, O'Reilly Ciara E, Phillips Stuart M, Tarnopolsky Mark A, Parise Gianni
Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada L8S 4L8.
J Physiol. 2008 Nov 15;586(22):5549-60. doi: 10.1113/jphysiol.2008.160176. Epub 2008 Sep 25.
Muscle regeneration following injury is dependent on the ability of muscle satellite cells to activate, proliferate and fuse with damaged fibres. This process is controlled by the myogenic regulatory factors (MRF). Little is known about the temporal relation of the MRF with the expression of known myogenic growth factors (i.e. IGF-1) in humans following muscle damage. Eight subjects (20.6 +/- 2.1 years; 81.4 +/- 9.8 kg) performed 300 lengthening contractions (180 deg s(-1)) of their knee extensors in one leg on a dynamometer. Blood and muscle samples were collected before and at 4 (T4), 24 (T24), 72 (T72) and 120 h (T120) post-exercise. Mechano growth factor (MGF), IGF-1Ea and IGF-1Eb mRNA were quantified. Serum IGF-1 did not change over the post-exercise time course. IGF-1Ea and IGF-1Eb mRNA increased approximately 4- to 6-fold by T72 (P < 0.01) and MGF mRNA expression peaked at T24 (P = 0.005). MyoD mRNA expression increased approximately 2-fold at T4 (P < 0.05). Myf5 expression peaked at T24 (P < 0.05), while MRF4 and myogenin mRNA expression peaked at T72 (P < 0.05). Myf5 expression strongly correlated with the increase in MGF mRNA (r(2) = 0.83; P = 0.03), while MRF4 was correlated with both IGF-1Ea and -Eb (r(2) = 0.90; r(2) = 0.81, respectively; P < 0.05). Immunofluorescence analysis showed IGF-1 protein expression localized to satellite cells at T24, and to satellite cells and the myofibre at T72 and T120; IGF-1 was not detected at T0 or T4. These results suggest that the temporal response of MGF is probably related to the activation/proliferation phase of the myogenic programme as marked by an increase in both Myf5 and MyoD, while IGF-1Ea and -Eb may be temporally related to differentiation as marked by an increase in MRF4 and myogenin expression following acute muscle damage.
损伤后的肌肉再生取决于肌肉卫星细胞激活、增殖并与受损纤维融合的能力。这一过程由生肌调节因子（MRF）控制。关于肌肉损伤后人体中MRF与已知生肌生长因子（即IGF-1）表达的时间关系，目前所知甚少。八名受试者（20.6±2.1岁；81.4±9.8千克）在测力计上对其一条腿的膝伸肌进行300次延长收缩（180度/秒）。在运动前以及运动后4小时（T4）、24小时（T24）、72小时（T72）和120小时（T120）采集血液和肌肉样本。对机械生长因子（MGF）、IGF-1Ea和IGF-1Eb的mRNA进行定量分析。运动后血清IGF-1在整个时间过程中没有变化。到T72时，IGF-1Ea和IGF-1Eb的mRNA增加了约4至6倍（P<0.01），MGF的mRNA表达在T24时达到峰值（P = 0.005）。MyoD的mRNA表达在T4时增加了约2倍（P<0.05）。Myf5的表达在T24时达到峰值（P<0.05），而MRF4和肌细胞生成素的mRNA表达在T72时达到峰值（P<0.05）。Myf5的表达与MGF的mRNA增加密切相关（r² = 0.83；P = 0.03），而MRF4与IGF-1Ea和-Eb均相关（r²分别为0.90和0.81；P<0.05）。免疫荧光分析显示，IGF-1蛋白表达在T24时定位于卫星细胞，在T72和T120时定位于卫星细胞和肌纤维；在T0或T4时未检测到IGF-1。这些结果表明，MGF的时间反应可能与以Myf5和MyoD增加为标志的生肌程序的激活/增殖阶段有关，而IGF-1Ea和-Eb可能在时间上与急性肌肉损伤后以MRF4和肌细胞生成素表达增加为标志的分化有关。
