Basic fibroblast growth factor stimulates the proliferation of human dermal fibroblasts via the ERK1/2 and JNK pathways.
BACKGROUND
Basic fibroblast growth factor (bFGF, FGF-2) has been described as a multipotent cytokine that regulates cell growth as well as differentiation, matrix composition, chemotaxis, cell adhesion and migration in numerous cell types. It is known that bFGF stimulates proliferation of cultured fibroblasts. However, the detailed mechanism of fibroblast proliferation induced by bFGF in vitro still remains to be elucidated. Objectives We investigated the precise effects of bFGF on fibroblast proliferation and the signalling pathways responsible for bFGF-induced proliferation in cultured human dermal fibroblasts (HDFs).


METHODS
HDFs were cultured with bFGF in the presence or absence of specific inhibitors against MAPK signalling pathways including ERK, JNK and p38. The number of cells was counted and immunoblotting findings were examined for the activation of ERK1/2 and JNK. Furthermore, the inhibitory effects of ERK1, ERK2 and JNK1 were proven by the transfection of siRNA.


RESULTS
bFGF increased the number of HDFs in a dose- and time-dependent manner. The bFGF-induced proliferation was suppressed by the MEK inhibitors PD98059 and U0126, and the JNK inhibitor SP600125. bFGF increased the phosphorylation levels of ERK1/2 and JNK1. Treatment with ERK1, ERK2 or JNK1 siRNA significantly inhibited bFGF-induced proliferation.


CONCLUSIONS
This study indicates that ERK1/2 and JNK pathways play an important role in the bFGF-mediated effect in HDFs. This study also suggests that controlling ERK1/2 and/or JNK signalling may therefore be a new therapeutic approach for the treatment of chronic and untreatable skin ulcers.
Makino
T
T
Department of Dermatology and Plastic Surgery, Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
Jinnin
M
M
Muchemwa
F C
FC
Fukushima
S
S
Kogushi-Nishi
H
H
Moriya
C
C
Igata
T
T
Fujisawa
A
A
Johno
T
T
Ihn
H
H
D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D012867:Skin / Q000166:cytology
D016222:Fibroblast Growth Factor 2; D048031:JNK Mitogen-Activated Protein Kinases