Sharma M, Kambadur R, Matthews K G, Somers W G, Devlin G P, Conaglen J V, Fowke P J, Bass J J
Growth Physiology, AgResearch, Ruakura, Hamilton, New Zealand.
J Cell Physiol. 1999 Jul;180(1):1-9. doi: 10.1002/(SICI)1097-4652(199907)180:1<1::AID-JCP1>3.0.CO;2-V.
Myostatin is a secreted growth and differentiating factor (GDF-8) that belongs to the transforming growth factor-beta (TGF-beta) superfamily. Targeted disruption of the myostatin gene in mice and a mutation in the third exon of the myostatin gene in double-muscled Belgian Blue cattle breed result in skeletal muscle hyperplasia. Hence, myostatin has been shown to be involved in the regulation of skeletal muscle mass in both mice and cattle. Previous published reports utilizing Northern hybridization had shown that myostatin expression was seen exclusively in skeletal muscle. A significantly lower level of myostatin mRNA was also reported in adipose tissue. Using a sensitive reverse transcription-polymerase chain reaction (RT-PCR) technique and Western blotting with anti-myostatin antibodies, we show that myostatin mRNA and protein are not restricted to skeletal muscle. We also show that myostatin expression is detected in the muscle of both fetal and adult hearts. Sequence analysis reveals that the Belgian Blue heart myostatin cDNA sequence contains an 11 nucleotide deletion in the third exon that causes a frameshift that eliminates virtually all of the mature, active region of the protein. Anti-myostatin immunostaining on heart sections also demonstrates that myostatin protein is localized in Purkinje fibers and cardiomyocytes in heart tissue. Furthermore, following myocardial infarction, myostatin expression is upregulated in the cardiomyocytes surrounding the infarct area. Given that myostatin is expressed in fetal and adult hearts and that myostatin expression is upregulated in cardiomyocytes after the infarction, myostatin could play an important role in cardiac development and physiology.
肌肉生长抑制素是一种分泌型生长和分化因子（GDF - 8），属于转化生长因子β（TGF - β）超家族。在小鼠中对肌肉生长抑制素基因进行靶向破坏，以及在双肌比利时蓝牛品种中肌肉生长抑制素基因的第三个外显子发生突变，都会导致骨骼肌增生。因此，已证明肌肉生长抑制素参与小鼠和牛骨骼肌质量的调节。先前利用Northern杂交发表的报告显示，肌肉生长抑制素的表达仅在骨骼肌中可见。也有报告称脂肪组织中肌肉生长抑制素mRNA水平显著较低。使用灵敏的逆转录 - 聚合酶链反应（RT - PCR）技术和抗肌肉生长抑制素抗体进行蛋白质印迹分析，我们发现肌肉生长抑制素mRNA和蛋白质并不局限于骨骼肌。我们还发现，在胎儿和成年心脏的肌肉中都能检测到肌肉生长抑制素的表达。序列分析表明，比利时蓝牛心脏肌肉生长抑制素cDNA序列在第三个外显子中有一个11个核苷酸的缺失，这导致了移码突变，几乎消除了该蛋白质所有成熟的活性区域。对心脏切片进行抗肌肉生长抑制素免疫染色也表明，肌肉生长抑制素蛋白定位于心脏组织中的浦肯野纤维和心肌细胞中。此外，心肌梗死后，梗死区域周围的心肌细胞中肌肉生长抑制素的表达上调。鉴于肌肉生长抑制素在胎儿和成年心脏中表达，且在梗死后心肌细胞中其表达上调，肌肉生长抑制素可能在心脏发育和生理过程中发挥重要作用。
