研究人員一直對(duì)一種被稱(chēng)作肌肉生長(zhǎng)抑制素(myostatin, MSN)的肌肉系統(tǒng)蛋白特別感興趣,，這是因?yàn)閷?duì)患有肌肉疾病的病人而言,，它是一種潛在的治療靶標(biāo),。盡管科學(xué)家們已經(jīng)知道很多關(guān)于MSN如何影響肌肉生長(zhǎng)的信息,，但是他們?cè)谒鼘?duì)哪種肌肉細(xì)胞發(fā)揮作用方面一直未達(dá)成共識(shí),。在一項(xiàng)新研究中,，包括美國(guó)卡內(nèi)基科學(xué)研究所研究員Chen-Ming Fan和Christoph Lepper在內(nèi)的一個(gè)研究小組將范圍縮小到一種可能類(lèi)型的肌肉細(xì)胞,。2012年8月6日,，他們的研究成果在線(xiàn)發(fā)表在PNAS期刊上,。
已知MSN抑制肌肉生長(zhǎng)，并且它的作用在包括奶牛,、羊,、狗、人類(lèi)和小鼠在內(nèi)的多種哺乳動(dòng)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(biāo),。
不過(guò),，科學(xué)家們?cè)贛SN作用于哪種類(lèi)型的肌肉細(xì)胞上一直存在很大分歧：是被稱(chēng)作肌纖維的纖維狀肌肉細(xì)胞，還是被稱(chēng)作衛(wèi)星細(xì)胞的肌肉干細(xì)胞,。一些人似乎認(rèn)為MSN作用于衛(wèi)星細(xì)胞,，另外一些人則認(rèn)為MSN作用于肌纖維。
為此,，研究人員利用多種技術(shù)---基因技術(shù)和藥理學(xué)方法---來(lái)開(kāi)展實(shí)驗(yàn),，并且確定抑制MSN導(dǎo)致的肌肉生長(zhǎng)并不顯著性參與衛(wèi)星細(xì)胞整合到肌纖維之中。
這項(xiàng)發(fā)現(xiàn)對(duì)MSN可能被用作一種臨床靶標(biāo)產(chǎn)生重要影響,。突出問(wèn)題在于當(dāng)病人衛(wèi)星細(xì)胞被全部耗盡時(shí),，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(xì)胞被認(rèn)為能夠彌補(bǔ)退化的肌肉細(xì)胞,，但是隨著時(shí)間的推移,，這種疾病能夠?qū)е录∪飧杉?xì)胞池耗盡。這項(xiàng)研究表明對(duì)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.
