Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting.
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.
Gonzalez-Cadavid
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Division of Endocrinology, Charles R. Drew University, Los Angeles, CA 90059, USA. ncadavid@ucla.edu
Taylor
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WE
Yarasheski
K
K
Sinha-Hikim
I
I
Ma
K
K
Ezzat
S
S
Shen
R
R
Lalani
R
R
Asa
S
S
Mamita
M
M
Nair
G
G
Arver
S
S
Bhasin
S
S
D000328:Adult; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002417:Cattle; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2; D003001:Cloning, Molecular; D006224:Cricetinae; D005091:Exons / Q000235:genetics; D015658:HIV Infections / Q000235:genetics* / Q000503:physiopathology; D019247:HIV Wasting Syndrome / Q000235:genetics* / Q000503:physiopathology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000503:physiopathology; D055435:Myostatin; D017422:Sequence Analysis, DNA; D016212:Transforming Growth Factor beta / Q000235:genetics*
C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin; D016212:Transforming Growth Factor beta