title: Perlecan deficiency causes muscle hypertrophy, a decrease in myostatin expression, and changes in muscle fiber composition.
abstract: Perlecan is a component of the basement membrane that surrounds skeletal muscle. The aim of the present study is to identify the role of perlecan in skeletal muscle hypertrophy and myostatin signaling, with and without mechanical stress, using a mouse model (Hspg2(-/-)-Tg) deficient in skeletal muscle perlecan. We found that myosin heavy chain (MHC) type IIb fibers in the tibialis anterior (TA) muscle of Hspg2(-/-)-Tg mice had a significantly increased fiber cross-sectional area (CSA) compared to control (WT-Tg) mice. Hspg2(-/-)-Tg mice also had an increased number of type IIx fibers in the TA muscle. Myostatin and its type I receptor (ALK4) expression was substantially decreased in the Hspg2(-/-)-Tg TA muscle. Myostatin-induced Smad activation was also reduced in a culture of myotubes from the Hspg2(-/-)-Tg muscle, suggesting that myostatin expression and its signaling were decreased in the Hspg2(-/-)-Tg muscle. To examine the effects of mechanical overload or unload on fast and slow muscles in Hspg2(-/-)-Tg mice, we performed tenotomy of the plantaris (fast) muscle and the soleus (slow) muscle. Mechanical overload on the plantaris muscle of Hspg2(-/-)-Tg mice significantly increased wet weights compared to those of control mice, and unloaded plantaris muscles of Hspg2(-/-)-Tg mice caused less decrease in wet weights compared to those of control mice. The decrease in myostatin expression was significantly profound in the overloaded plantaris muscle of Hspg2(-/-)-Tg mice, compared with that of control mice. In contrast, overloading the soleus muscle caused no changes in either type of muscle. These results suggest that perlecan is critical for maintaining fast muscle mass and fiber composition, and for regulating myostatin signaling.
authors.affiliation: Research Institute for Diseases of Old Age, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Xu
authors.forename: Naoki
authors.initials: N
authors.lastname: Ichikawa
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kosaki
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Yamada
authors.forename: Takako
authors.initials: T
authors.lastname: Sasaki
authors.forename: Lynn Y
authors.initials: LY
authors.lastname: Sakai
authors.forename: Hisashi
authors.initials: H
authors.lastname: Kurosawa
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
authors.forename: Eri
authors.initials: E
authors.lastname: Arikawa-Hirasawa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019812:Heparan Sulfate Proteoglycans / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006984:Hypertrophy / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000502:physiology; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology; D009132:Muscles / Q000378:metabolism*; D009142:Musculoskeletal Physiological Phenomena; D055435:Myostatin / Q000378:metabolism*; D058971:Tenotomy; D019076:Transgenes
chemical_list: D019812:Heparan Sulfate Proteoglycans; D055435:Myostatin; C071927:perlecan