title: Hepatocyte growth factor affects satellite cell activation and differentiation in regenerating skeletal muscle.
abstract: Hepatocyte growth factor (HGF) is the only known growth factor that activates quiescent satellite cells in skeletal muscle. We hypothesized that local delivery of HGF may enhance regeneration after trauma by increasing the number of myoblasts available for restoring normal tissue architecture. Injection of HGF into muscle at the time of injury increases myoblast number but does not enhance tissue repair as determined using quantitative histological analyses. Rather, depending on the dose and the timing of HGF administration relative to the injury, regeneration can be inhibited. The greatest inhibitory effect is observed when HGF is administered on the day of injury and continued for 3 days, corresponding to the time when satellite cell activation, proliferation, and early differentiation normally occur. To establish a mechanism for this inhibition, we show that HGF can act directly on primary muscle cells to block differentiation. These results demonstrate that 1) exogenous HGF synergizes with factors in damaged muscle to increase myoblast number, 2) regeneration is not regulated solely by myoblast number, and 3) HGF inhibits muscle differentiation both in vitro and in vivo.
authors.affiliation: Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: Miller
authors.forename: D
authors.initials: D
authors.lastname: Thaloor
authors.forename: S
authors.initials: S
authors.lastname: Matteson
authors.forename: G K
authors.initials: GK
authors.lastname: Pavlath
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000293:injuries / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012038:Regeneration / Q000502:physiology*; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; D017228:Hepatocyte Growth Factor