Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting
Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting
复制标题
DOI：
10.1073/pnas.95.25.14938
复制
发表时间：
1998-12-08
影响因子：
11.1
通讯作者：
Bhasin, S
中科院分区：
文献类型：
--
作者：
Gonzalez-Cadavid, NF;Taylor, WE;Bhasin, S
肌生长抑制素是转化生长因子β超家族的成员，是骨骼肌生长的遗传决定因子。具有肌生长抑制素失活突变的小鼠和牛具有显著的肌肉肥大。然而，目前尚不清楚肌肉生长抑制素是否调节成年男性骨骼肌的生长，以及肌肉生长抑制素表达的增加是否有助于慢性疾病中的消瘦。我们检验了这样的假设，即肌肉生长抑制素的表达与人体的无脂肪质量呈负相关，而肌肉生长抑制素基因的表达增加与艾滋病消瘦综合征男性的体重减轻有关。因此，我们克隆了人肌肉生长抑制素基因和cDNA，并研究了该基因在健康和HIV感染男性骨骼肌和血清中的表达。肌生长抑制素基因包含三个外显子和两个内含子，定位于染色体区域2q33.2，具有三个假定的转录起始位点，并且转录为编码375-aa前体蛋白的3.1-kb mRNA种类。肌生长抑制素在人骨骼肌中独特地表达为26-kDa成熟糖蛋白（肌生长抑制素免疫反应性蛋白）并分泌到血浆中。肌生长抑制素免疫反应性在人骨骼肌中的1型和2型纤维中均可检测到。与健康男性相比，体重减轻的HIV感染男性的血清和肌内肌生长抑制素免疫反应性蛋白的浓度增加，并且与无脂肪质量指数呈负相关。这些数据支持以下假设：肌生长抑制素是成年男性骨骼肌生长的衰减剂，并且有助于HIV感染男性的肌肉萎缩。
Myostatin, a member of the transforming growth factor-beta superfamily, is a genetic determinant of skeletal muscle growth. Mice and cattle with inactivating mutations of myostatin have marked muscle hypertrophy. However, it is not known whether myostatin regulates skeletal muscle growth in adult men and whether increased myostatin expression contributes to wasting in chronic illness. We examined the hypothesis that myostatin expression correlates inversely with fat-free mass in humans and that increased expression of the myostatin gene is associated with weight loss in men with AIDS wasting syndrome. We therefore cloned the human myostatin gene and cDNA and examined the gene's expression in the skeletal muscle and serum of healthy and HIV-infected men. The myostatin gene comprises three exons and two introns, maps to chromosomal region 2q33.2, has three putative transcription initiation sites, and is transcribed as a 3.1-kb mRNA species that encodes a 375-aa precursor protein. Myostatin is expressed uniquely in the human skeletal muscle as a 26-kDa mature glycoprotein (myostatin-immunoreactive protein) and secreted into the plasma. Myostatin immunoreactivity is detectable in human skeletal muscle in both type 1 and 2 fibers. The serum and intramuscular concentrations of myostatin-immunoreactive protein are increased in HIV-infected men with weight loss compared,vith healthy men and correlate inversely with fat-free mass index These data support the hypothesis that myostatin is an attenuator of skeletal muscle growth in adult men and contributes to muscle wasting in HIV-infected men.