研究人員一直對一種被稱作肌肉生長抑制素(myostatin, MSN)的肌肉系統(tǒng)蛋白特別感興趣，這是因為對患有肌肉疾病的病人而言,，它是一種潛在的治療靶標,。盡管科學家們已經(jīng)知道很多關于MSN如何影響肌肉生長的信息,，但是他們在它對哪種肌肉細胞發(fā)揮作用方面一直未達成共識。在一項新研究中,，包括美國卡內(nèi)基科學研究所研究員Chen-Ming Fan和Christoph Lepper在內(nèi)的一個研究小組將范圍縮小到一種可能類型的肌肉細胞,。2012年8月6日，他們的研究成果在線發(fā)表在PNAS期刊上,。
已知MSN抑制肌肉生長,，并且它的作用在包括奶牛、羊,、狗,、人類和小鼠在內(nèi)的多種哺乳動物中都是相同的。在缺乏MSN的突變小鼠體內(nèi),，肌肉質(zhì)量幾乎是正常小鼠的2倍,。這種性質(zhì)使得它成為一種有吸引人的潛在藥物靶標。
不過,，科學家們在MSN作用于哪種類型的肌肉細胞上一直存在很大分歧：是被稱作肌纖維的纖維狀肌肉細胞,，還是被稱作衛(wèi)星細胞的肌肉干細胞,。一些人似乎認為MSN作用于衛(wèi)星細胞，另外一些人則認為MSN作用于肌纖維,。
為此,，研究人員利用多種技術---基因技術和藥理學方法---來開展實驗，并且確定抑制MSN導致的肌肉生長并不顯著性參與衛(wèi)星細胞整合到肌纖維之中,。
這項發(fā)現(xiàn)對MSN可能被用作一種臨床靶標產(chǎn)生重要影響,。突出問題在于當病人衛(wèi)星細胞被全部耗盡時，靶向MSN的藥物如何發(fā)揮作用,。比如,，在肌肉萎縮癥(muscular dystrophy)中，在疾病初始階段,，衛(wèi)星細胞被認為能夠彌補退化的肌肉細胞,，但是隨著時間的推移，這種疾病能夠?qū)е录∪飧杉毎睾谋M,。這項研究表明對這種疾病的病人而言,，MSN抑制劑仍然可能有益處。(生物谷：Bioon.com)
本文編譯自Possible muscle disease therapeutic target found
doi: 10.1073/pnas.1206410109
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Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway
Se-Jin Leea,1, Thanh V. Huynha, Yun-Sil Leea, Suzanne M. Sebalda, Sarah A. Wilcox-Adelmanb, Naoki Iwamoric, Christoph Lepperd, Martin M. Matzukc,e,f,g,h, and Chen-Ming Fan
Myostatin and activin A are structurally related secreted proteins that act to limit skeletal muscle growth. The cellular targets for myostatin and activin A in muscle and the role of satellite cells in mediating muscle hypertrophy induced by inhibition of this signaling pathway have not been fully elucidated. Here we show that myostatin/activin A inhibition can cause muscle hypertrophy in mice lacking either syndecan4 or Pax7, both of which are important for satellite cell function and development. Moreover, we show that muscle hypertrophy after pharmacological blockade of this pathway occurs without significant satellite cell proliferation and fusion to myofibers and without an increase in the number of myonuclei per myofiber. Finally, we show that genetic ablation of Acvr2b, which encodes a high-affinity receptor for myostatin and activin A specifically in myofibers is sufficient to induce muscle hypertrophy. All of these findings are consistent with satellite cells playing little or no role in myostatin/activin A signaling in vivo and render support that inhibition of this signaling pathway can be an effective therapeutic approach for increasing muscle growth even in disease settings characterized by satellite cell dysfunction.
