Increased HGF and c-Met in muscle tissues of polymyositis and dermatomyositis patients: beneficial roles of HGF in muscle regeneration.
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.
Sugiura
Tomoko
T
Institute of Rheumatology, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
Kawaguchi
Yasushi
Y
Soejima
Makoto
M
Katsumata
Yasuhiro
Y
Gono
Takahisa
T
Baba
Sayumi
S
Kawamoto
Manabu
M
Murakawa
Yohko
Y
Yamanaka
Hisashi
H
Hara
Masako
M
D000199:Actins / Q000235:genetics; D019002:CD56 Antigen / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D055513:Connective Tissue Growth Factor / Q000235:genetics; D003882:Dermatomyositis / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D017228:Hepatocyte Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D017570:MyoD Protein / Q000235:genetics; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics; D017285:Polymyositis / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D000076202:c-Mer Tyrosine Kinase
C541116:ACTA2 protein, human; D000199:Actins; C526317:CCN2 protein, human; D019002:CD56 Antigen; D024042:Collagen Type I; C066855:HGF protein, human; C497417:MYF5 protein, human; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D051787:Myogenic Regulatory Factor 5; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D055513:Connective Tissue Growth Factor; D017228:Hepatocyte Growth Factor; D003907:Dexamethasone; C097072:MERTK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase