The molecular chaperone HSP47 rapidly senses gravitational changes in myoblasts.
Skeletal muscle unloading induced by spaceflight or bed rest leads to muscle atrophy. It is unclear how muscle atrophy is caused and how muscles respond to microgravity. We addressed the response of collagen and its chaperone system to gravitational forces. We show here that expression of HSP47, a collagen-specific molecular chaperone, responds to gravitational changes, including microgravity and hypergravity in vitro and in vivo. By using the method hindlimb suspension of rats, which mimics microgravity conditions, we demonstrated that the expression of Hsp47 mRNA decreased within 1 day and the mRNA levels of collagen types I and IV were subsequently reduced. In contrast, hypergravity stimulated HSP47 expression. HSP47 and collagen types I and IV were localized intracellularly in the endoplasmic reticulum and/or Golgi apparatus of myoblasts, as expected. Intriguingly, Hsp47 mRNA levels in cultured myoblasts increased significantly with hypergravity treatment at 40G for 2 h, and decreased with microgravity treatment at almost 0G for 1-2 h. Collagen mRNA levels were also altered, although changes were slower and less pronounced compared with those for HSP47. The gravity-regulated HSP47 may play a role in the maintenance of the extracellular matrix by modulating collagen production at the primary stage of adaptation.
Oguro
Asami
A
Department of Life Sciences, The Graduate School of Arts and Sciences, The University of Tokyo, Tokyo 153-8902, Japan.
Sakurai
Takashi
T
Fujita
Yoshinobu
Y
Lee
Sachiko
S
Kubota
Hiroshi
H
Nagata
Kazuhiro
K
Atomi
Yoriko
Y
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D006112:Gravitation; D050958:HSP47 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism*; D019417:Hindlimb Suspension / Q000502:physiology; D018471:Hypergravity; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D032448:Myoblasts, Skeletal / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D018474:Weightlessness Simulation
D024042:Collagen Type I; D024141:Collagen Type IV; D017931:DNA Primers; D050958:HSP47 Heat-Shock Proteins; D012333:RNA, Messenger; C494662:Serpinh1 protein, rat; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha