Perlecan deficiency causes muscle hypertrophy, a decrease in myostatin expression, and changes in muscle fiber composition

Zhuo Xu, Naoki Ichikawa, Keisuke Kosaki, Yoshihiko Yamada, Takako Sasaki, Lynn Sakai, Hisashi Kurosawa, Nobutaka Hattori, Eri Arikawa-Hirasawa

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)461-470
Number of pages10
JournalMatrix Biology
Volume29
Issue number6
DOIs
StatePublished - Jul 1 2010
Externally publishedYes

Fingerprint

Myostatin
Hypertrophy
Skeletal Muscle
Muscles
perlecan
Tenotomy
Weights and Measures
Mechanical Stress
Myosin Heavy Chains
Skeletal Muscle Fibers
Basement Membrane

Keywords

  • Mechanical stress
  • Muscle hypertrophy
  • Myostatin
  • Perlecan

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Perlecan deficiency causes muscle hypertrophy, a decrease in myostatin expression, and changes in muscle fiber composition. / Xu, Zhuo; Ichikawa, Naoki; Kosaki, Keisuke; Yamada, Yoshihiko; Sasaki, Takako; Sakai, Lynn; Kurosawa, Hisashi; Hattori, Nobutaka; Arikawa-Hirasawa, Eri.

In: Matrix Biology, Vol. 29, No. 6, 01.07.2010, p. 461-470.

Research output: Contribution to journalArticle

Xu, Z, Ichikawa, N, Kosaki, K, Yamada, Y, Sasaki, T, Sakai, L, Kurosawa, H, Hattori, N & Arikawa-Hirasawa, E 2010, 'Perlecan deficiency causes muscle hypertrophy, a decrease in myostatin expression, and changes in muscle fiber composition', Matrix Biology, vol. 29, no. 6, pp. 461-470. https://doi.org/10.1016/j.matbio.2010.06.001
Xu, Zhuo ; Ichikawa, Naoki ; Kosaki, Keisuke ; Yamada, Yoshihiko ; Sasaki, Takako ; Sakai, Lynn ; Kurosawa, Hisashi ; Hattori, Nobutaka ; Arikawa-Hirasawa, Eri. / Perlecan deficiency causes muscle hypertrophy, a decrease in myostatin expression, and changes in muscle fiber composition. In: Matrix Biology. 2010 ; Vol. 29, No. 6. pp. 461-470.
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