Increased HGF and c-Met in muscle tissues of polymyositis and dermatomyositis patients: beneficial roles of HGF in muscle regeneration

Tomoko Sugiura; Yasushi Kawaguchi; Makoto Soejima; Yasuhiro Katsumata; Takahisa Gono; Sayumi Baba; Manabu Kawamoto; Yohko Murakawa; Hisashi Yamanaka; Masako Hara

doi:10.1016/j.clim.2010.04.015

Increased HGF and c-Met in muscle tissues of polymyositis and dermatomyositis patients: beneficial roles of HGF in muscle regeneration

Clin Immunol. 2010 Sep;136(3):387-99. doi: 10.1016/j.clim.2010.04.015. Epub 2010 May 23.

Authors

Tomoko Sugiura¹, Yasushi Kawaguchi, Makoto Soejima, Yasuhiro Katsumata, Takahisa Gono, Sayumi Baba, Manabu Kawamoto, Yohko Murakawa, Hisashi Yamanaka, Masako Hara

Affiliation

¹ Institute of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.

PMID: 20580899
DOI: 10.1016/j.clim.2010.04.015

Abstract

We investigated the expression of hepatocyte growth factor (HGF), which has mitogenic and anti-fibrotic activities, in muscle tissue of polymyositis/dermatomyositis (PM/DM) patients, as well as its functional roles in cultured myoblasts. Immunohistochemistry in muscle from PM/DM patients revealed that HGF was expressed predominantly on infiltrating mononuclear cells and that muscle cells expressed the receptor c-met. Cultured myoblasts produced HGF; which was increased by IL-1alpha but suppressed by TGF-beta and dexamethasone. Exogenous HGF induced myoblast proliferation and reduced procollagen type I production. Furthermore, HGF enhanced the gene expression of muscle regulatory factors MyoD and Myf5, while suppressing expression of fibrosis-related genes, connective tissue growth factor and alpha-smooth muscle actin. Although dexamethasone showed contrasting effects to HGF on the expression of these genes, co-treatment with HGF ameliorated the effects of dexamethasone. Taking the beneficial roles of HGF into consideration, administration of HGF might contribute to muscle regeneration in PM/DM especially under corticosteroid treatment.

MeSH terms

Actins / genetics
CD56 Antigen / metabolism
Case-Control Studies
Cell Proliferation / drug effects
Cells, Cultured
Collagen Type I / biosynthesis
Connective Tissue Growth Factor / genetics
Dermatomyositis / metabolism*
Dexamethasone / pharmacology
Gene Expression / drug effects
Hepatocyte Growth Factor / metabolism*
Hepatocyte Growth Factor / pharmacology
Humans
Immunohistochemistry
MyoD Protein / genetics
Myoblasts, Skeletal / cytology
Myoblasts, Skeletal / drug effects
Myoblasts, Skeletal / metabolism
Myogenic Regulatory Factor 5 / genetics
Polymyositis / metabolism*
Proto-Oncogene Proteins / metabolism*
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptor Protein-Tyrosine Kinases / metabolism*
Recombinant Proteins / pharmacology
Regeneration / drug effects
Regeneration / genetics
Regeneration / physiology
c-Mer Tyrosine Kinase

Substances

ACTA2 protein, human
Actins
CCN2 protein, human
CD56 Antigen
Collagen Type I
HGF protein, human
MYF5 protein, human
MyoD Protein
MyoD1 myogenic differentiation protein
Myogenic Regulatory Factor 5
Proto-Oncogene Proteins
RNA, Messenger
Recombinant Proteins
Connective Tissue Growth Factor
Hepatocyte Growth Factor
Dexamethasone
MERTK protein, human
Receptor Protein-Tyrosine Kinases
c-Mer Tyrosine Kinase