Transforming growth factor-beta, basic fibroblast growth factor, and platelet-derived growth factor-BB interact to affect proliferation of clonally derived porcine satellite cells.
Transforming growth factor beta-1 (TGF-beta) stimulated porcine satellite cell proliferation in basal serum-free medium by 25%, but inhibited growth in serum-containing medium by 58%. The effect of TGF-beta on cell proliferation in serum-free medium was examined in combination with the following human recombinant growth factors: platelet-derived growth factor-BB (PDGF), basic fibroblast growth factor (FGF), insulin-like growth factor I (IGF-I), and epidermal growth factor (EGF). TGF-beta inhibited PDGF-stimulated proliferation, enhanced FGF-stimulated proliferation, and had no effect on proliferation stimulated by IGF-I. The response of satellite cells to EGF and TGF-beta in serum-free medium was not different than TGF-beta alone. TGF-beta depressed proliferation stimulated by the following combinations of two growth factors: PDGF and IGF-I, PDGF and EGF, PDGF and FGF, and IGF-I and EGF. In combination with IGF-I and FGF, TGF-beta did not affect proliferation. TGF-beta inhibited proliferation stimulated by the combination of PDGF, EGF, and IGF-I, but had no effect on proliferation stimulated by combinations of three growth factors that included FGF. FGF stimulated proliferation in Minimum Essential Medium containing 10% porcine serum (MEM-10% PS) by 13% above control. When the combination of TGF-beta and FGF was added to MEM-10% PS, a 78% increase in proliferation was observed. Polyclonal antihuman PDGF-AB (this form neutralizes PDGF-AA, AB, and BB) reduced proliferation in MEM-10% PS by 44%. The combination of TGF-beta and anti-PDGF-AB reduced proliferation by 59%, indicating the effects were not additive. These data indicate that: (1) FGF and TGF-beta interact to increase proliferation of clonally derived porcine satellite cells, and (2) the inhibitory effect of TGF-beta on proliferation of clonally derived porcine satellite cells can be primarily attributed to a reduction in the mitogenic effects of PDGF.
Cook
D R
DR
Department of Animal Science, Michigan State University, East Lansing 48824.
Doumit
M E
ME
Merkel
R A
RA
D000818:Animals; D000077214:Becaplermin; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004347:Drug Interactions; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D009132:Muscles / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins / Q000494:pharmacology; D013552:Swine / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin