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Cell Metab:响应因子(Srf)是肌肉强壮生长关键要素

2012-01-06 MedSci原创 MedSci原创

日前,研究人员鉴定了一个肌肉强壮发生的关键要素.这个要素产生在工作的肌肉纤维中,明显在告诉周边的肌肉干细胞是时间“要更高地”增殖和加入.相关研究论文"Srf-Dependent Paracrine Signals Produced by Myofibers Control Satellite Cell-Mediated Skeletal Muscle Hypertrophy"发表在1月4日的Cel

日前,研究人员鉴定了一个肌肉强壮发生的关键要素.这个要素产生在工作的肌肉纤维中,明显在告诉周边的肌肉干细胞是时间“要更高地”增殖和加入.相关研究论文"Srf-Dependent Paracrine Signals Produced by Myofibers Control Satellite Cell-Mediated Skeletal Muscle Hypertrophy"发表在1月4日的Cell Metabolism杂志上.

我们认为理所当然,但是事实上我们肌肉的成长,在我们使用它们时让它们变得颇为独特.换句话说,所谓的响应因子(Srf)转化工作的机械信号成一个化学信号.

“该信号来自肌肉纤维,控制这干细胞的行为和肌肉生长的参与,”法国国家健康与医学研究院的Athanassia Sotiropoulos说,“这是意想不到的,且十分有趣.”这也许为对付肌肉萎缩创造了新的途径.


Sotiropoulos的小组变得对Srf在肌肉中的作用感兴趣,部分是因为他们对小鼠和人类的最早研究表明Srf浓度随着年龄增加而下降.使得他们认为Srf可能是伴随衰老而发生肌肉萎缩的罪犯.

新发现支持这个观点,但是Srf不像研究人员所预期的那样发生作用.Srf在肌肉纤维内控制许多其他基因.Srf也出人意料地影响卫星干细胞的活动.新研究显示,肌肉纤维缺中缺乏Srf的小鼠当实验超载就不能够生长.因为卫星细胞没有获得增殖和融入这些已有肌纤维的信号.

Srf通过基因网络工作,包括已知的Cox2.这样提出了个有趣的可能性,通常利用Cox2抑制剂,想象布洛芬,也许会违背肌肉的生长或恢复,Sotiropoulos说.

她说,旨在调整这个网络因素的治疗可能被用于唤醒肌肉干细胞,并强化肌肉在衰老或长时间卧床休息等状况下的生长.大多数情况下,这种治疗更成功的指向不是Srf本身,Srf有多重角色,而是指向它的目标.

“很难找到Srf的一个有利的量,”她说,“它的目标,白介素和前列腺素,可以较容易操作.”

Srf-Dependent Paracrine Signals Produced by Myofibers Control Satellite Cell-Mediated Skeletal Muscle Hypertrophy

Aline Guerci, Charlotte Lahoute, Sophie Hébrard, Laura Collard, Dany Graindorge,et al.

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 rescue 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.

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    2012-01-13 维他命
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    2012-11-19 guojianrong
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    2012-10-15 一闲
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