Gonzalez-Cadavid N F, Taylor W E, Yarasheski K, Sinha-Hikim I, Ma K, Ezzat S, Shen R, Lalani R, Asa S, Mamita M, Nair G, Arver S, Bhasin S
Division of Endocrinology, Charles R. Drew University, Los Angeles, CA 90059, USA.
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14938-43. doi: 10.1073/pnas.95.25.14938.
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 with 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.
肌肉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素。肌肉生长抑制素发生失活突变的小鼠和牛会出现明显的肌肉肥大。然而，尚不清楚肌肉生长抑制素是否调节成年男性的骨骼肌生长，以及肌肉生长抑制素表达增加是否导致慢性病中的消瘦。我们检验了以下假设：在人类中，肌肉生长抑制素的表达与去脂体重呈负相关，且肌肉生长抑制素基因表达增加与艾滋病消瘦综合征男性的体重减轻有关。因此，我们克隆了人类肌肉生长抑制素基因和cDNA，并检测了该基因在健康男性和感染HIV男性的骨骼肌及血清中的表达。肌肉生长抑制素基因由三个外显子和两个内含子组成，定位于染色体区域2q33.2，有三个推定的转录起始位点，并转录为一种3.1 kb的mRNA，编码一个375个氨基酸的前体蛋白。肌肉生长抑制素仅在人类骨骼肌中表达为一种26 kDa的成熟糖蛋白（肌肉生长抑制素免疫反应蛋白），并分泌到血浆中。在人类骨骼肌的1型和2型纤维中均可检测到肌肉生长抑制素免疫反应性。与健康男性相比，体重减轻的感染HIV男性血清和肌肉内的肌肉生长抑制素免疫反应蛋白浓度升高，且与去脂体重指数呈负相关。这些数据支持以下假设：肌肉生长抑制素是成年男性骨骼肌生长的一种负调节因子，并导致感染HIV男性的肌肉消瘦。
