Myostatin antisense RNA-mediated muscle growth in normal and cancer cachexia mice.
Myostatin is a negative regulator of myogenesis, and inactivation of myostatin leads to muscle growth. Here we have used modified RNA oligonucleotides targeting the myostatin mRNA and examined the therapeutic potential in normal and cancer cachexia mouse models. We found that the RNA oligonucleotides could suppress the myostatin expression in vivo, leading to the increase in muscle growth both in normal and cachectic mice. We also established that the effect of myostatin inhibition caused by the RNA oligonucleotides may be through the MyoD pathway, as evidenced by a significant upregulation of MyoD expression. Taken together, these results demonstrate the feasibility using antisense strategy for the treatment of muscle wasting conditions.
Liu
C-M
CM
Molecular Virology Research Center, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Yang
Z
Z
Liu
C-W
CW
Wang
R
R
Tien
P
P
Dale
R
R
Sun
L-Q
LQ
D000251:Adenosine Triphosphatases / Q000032:analysis; D000284:Administration, Oral; D000818:Animals; D001483:Base Sequence; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western / Q000379:methods; D002100:Cachexia / Q000628:therapy*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000737:chemistry / Q000254:growth & development; D009133:Muscular Atrophy / Q000628:therapy*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D055435:Myostatin; D009368:Neoplasm Transplantation; D016372:RNA, Antisense / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics*
D015415:Biomarkers; C525912:Mstn protein, mouse; D017570:MyoD Protein; D055435:Myostatin; D016372:RNA, Antisense; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D000251:Adenosine Triphosphatases