We conducted this experimental study to analyze the relationship between
sphingosine-1-phosphate (S1P)-induced
mitogen-activated
protein (MAP)
kinase pathways and
keloid formation. We collected samples of the normal tissue and the
keloid tissue from 10 normal healthy individuals and 12 patients with
keloid scars, respectively. Then, we compared the level of
sphingosine-1-phosphate receptor (S1PR1/S1PR2)
mRNA/
protein expression between the normal tissue and the
keloid tissue. Moreover, we also compared the level of S1PR
protein expression, that of S1P-induced COL1A1 (
collagen Type I, α-1 chain) expression, that of S1P-induced JNK/ERK phosphorylation, that of S1P-induced COL1A1 expression following the treatment with 30 μM
PD98059 (ERK inhibitor) or 30 μM
SP600125 (JNK inhibitor) and that of S1P-induced COL1A1 expression following the treatment with W146 (S1PR1 inhibitor) or
JTE013 (S1PR2 inhibitor) between the normal fibroblasts and the
keloid fibroblasts. We found that the level of S1PR1/S1PR2
mRNA/
protein expression was significantly higher in the
keloid tissue as compared with the normal tissue. Our results also showed that the level of S1P-induced COL1A1 expression and that of S1P-induced JNK/ERK phosphorylation were significantly higher in the
keloid fibroblasts as compared with the normal ones (P < 0.05). Furthermore, there were significant decreases in the level of S1P-induced COL1A1 expression when the
keloid fibroblasts were treated with 30 μM
SP600125 or 30 μM
PD98059 and that of S1P-induced COL1A1 expression when the treated with 100 nM W146 or 100 nM
JTE013 (P < 0.05). Our results indicate that S1P-induced signal transduction is associated with increased
collagen synthesis via S1PR-mediated signaling pathways in the
keloid tissue.