Sulf1A and HGF regulate satellite-cell growth.
The role of Sulf1A, sulfation and hepatocyte growth factor (HGF) in satellite-cell growth was examined in an in vitro model of dissociated whole skeletal muscle fibres. Pax7-positive quiescent satellite cells express little or no Sulf1A but show rapid re-expression in regenerating myoblasts and myotubes, similar to embryonic muscle and in vitro satellite cells preceding asynchronous MyoD activation. Once activated, Sulf1A and MyoD re-expression persists up to 72 hours in most satellite cells under normal culture conditions and following moderate changes in sulfation, whereas Sulf1A neutralisation by antibodies not only enhances satellite-cell proliferation but also downregulates MyoD and Pax7 expression in a large proportion of the satellite cells. The HGF exposure also induces similar but even more pronounced changes characterised by variable sulfation levels and rapid downregulation of MyoD and Pax7 without myogenin activation in a sub-set of cells. This Pax7-MyoD-myogenin-negative sub-population expresses Sulf1A and Myf5. The transfer of all such satellite-cell progenies onto gelatin-coated-substratum re-activates MyoD and Pax7 gene expression in all cells, thus detecting a distinct sub-population of satellite cells. We conclude that HGF and fine-tuned sulfation levels are major contributory factors controlling satellite-cell growth by regulating the relative activities of actively proliferating and differentiating cells.
Gill
Roop
R
Department of Basic Sciences, The Royal Veterinary College, University of London, Royal College Street, London, NW1 0TU, UK.
Hitchins
Laura
L
Fletcher
Fenella
F
Dhoot
Gurtej K
GK
D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D051379:Mice; D018101:Mice, Inbred mdx; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000473:pathology; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism*; D051787:Myogenic Regulatory Factor 5 / Q000378:metabolism; D018008:Myogenin / Q000378:metabolism; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism* / Q000473:pathology; D015238:Sulfotransferases / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D013463:Sulfuric Acid Esters / Q000378:metabolism
D019138:Antibodies, Blocking; D015415:Biomarkers; C497418:Myf5 protein, mouse; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D051763:PAX7 Transcription Factor; D013463:Sulfuric Acid Esters; D017228:Hepatocyte Growth Factor; C486773:Sulf1 protein, mouse; D015238:Sulfotransferases