当前位置： SCI文献检索 > ACTA NEUROPATHOLOGICA期刊下所有文献 > Marked reduction of focal adhesion kinase, serum response factor and myocyte enhancer factor 2C, but increase in RhoA and myostatin in the hindlimb dy mouse muscles.

Marked reduction of focal adhesion kinase, serum response factor and myocyte enhancer factor 2C, but increase in RhoA and myostatin in the hindlimb dy mouse muscles.

Abstract：

:Laminin alpha2 (merosin)-deficient congenital muscular dystrophy (CMD) patients show progressive muscle fiber necrosis and ineffective muscle regeneration. This is probably due to decreased formation of multi nucleated myotubes resulting from a myoblast fusion defect. When receiving a mechanical signal from muscle membranes, a cascade of RhoA, focal adhesion kinase (FAK), and serum response factor (SRF) positively regulates myogenesis and muscle hypertrophy associated with functional overload. In contrast, myostatin, a potent negative regulator of skeletal muscle hypertrophy, appears to be up-regulated in the muscles of mdx mice, an animal model for Duchenne muscular dystrophy. Using Western blot and immunohistochemical analyses, we investigated the levels of RhoA, FAK, SRF, and myostatin in the skeletal muscles of dy mice. The amount of RhoA protein was increased in the hindlimb muscles of dy mice aged 12 weeks. At 12 weeks, FAK immunoreactivity was observed in the myonuclei and/or satellite cells of normal mice, but not of dy mice. SRF protein levels decreased markedly in the gastrocnemius and rectus femoris muscles of dy mice at 2 and 12 weeks. Several muscle fibers in normal mice possessed uniform SRF immunoreactivity in the cytoplasm. An SRF immunostaining pattern in muscle was not detected in dy mice. Western blot and the densitometric analysis showed a decreased amount of myocyte enhancer factor 2C (MEF2C) in hindlimb muscles of dy mice. Although slight myostatin immunoreactivity was observed in the nuclei of some normal mice, marked myostatin immunoreactivity was observed in the cytoplasm of mature dy mice myonuclei and/or satellite cells. A low expression of FAK, SRF and MEF2C in muscles of dy mice may inhibit postnatal muscle hypertrophy by fusing satellite cells with existing fibers. Enhancing myostatin protein would result in further atrophy and degeneration of muscle fiber in dy mice.

journal_name

Acta Neuropathol

journal_title

Acta neuropathologica

authors

Sakuma K,Nakao R,Inashima S,Hirata M,Kubo T,Yasuhara M

doi

10.1007/s00401-004-0884-5

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

241-9

issue

eissn

0001-6322

issn

1432-0533

journal_volume

108

pub_type

杂志文章

在线工具

Marked reduction of focal adhesion kinase, serum response factor and myocyte enhancer factor 2C, but increase in RhoA and myostatin in the hindlimb dy mouse muscles.