The role of leukemia inhibitory factor in skeletal muscle regeneration.
Although a number of cytokines have been implicated in tissue regeneration, it is unknown which ones actually function in vivo. Here, we use mice with a targeted mutation in the leukemia inhibitory factor (LIF) gene to examine the role of LIF in muscle regeneration. Using a muscle crush model, we show that muscle regeneration in LIF knockout mice is significantly, reduced compared to control littermates. Further, targeted infusion of LIF in both normal and LIF knockout animals stimulated muscle regeneration, but the stimulation observed was much greater in the mutant animals than in controls. In contrast, interleukin-6 and transforming growth factor-alpha, which also stimulate myoblast proliferation in vitro, had no effect on regeneration. These findings demonstrate directly that LIF is involved in regeneration of injured muscle and points to the use of LIF as a therapeutic agent in the treatment of neuromuscular disease.
Kurek
J B
JB
Melbourne Neuromuscular Research Centre, St. Vincent's Hospital, Fitzroy, Melbourne, Australia.
Bower
J J
JJ
Romanella
M
M
Koentgen
F
F
Murphy
M
M
Austin
L
L
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006131:Growth Inhibitors / Q000235:genetics / Q000493:pharmacokinetics*; D015850:Interleukin-6 / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000235:genetics / Q000493:pharmacokinetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000293:injuries / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012038:Regeneration / Q000187:drug effects* / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000493:pharmacokinetics
D006131:Growth Inhibitors; D015850:Interleukin-6; D007457:Iodine Radioisotopes; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D011994:Recombinant Proteins; D016211:Transforming Growth Factor alpha