Induction of connective tissue growth factor expression by sphingosylphosphorylcholine in cultured human skin fibroblasts.
Sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid metabolite that can enhance wound healing. In an effort to find downstream effectors of SPC, we performed microarray analysis and found that the expression of the gene for connective tissue growth factor (CTGF) was significantly affected in human skin fibroblasts cultured in vitro. Northern blot analysis showed that SPC markedly induced CTGF mRNA expression in a dose- and time-dependent manner. Consistent with this result, Western blot analysis also showed that SPC significantly induced the CTGF production. Pretreatment with cycloheximide did not prevent the CTGF induction by SPC, indicating that SPC stimulates CTGF mRNA expression without the increased synthesis of a regulatory protein. Inhibition by pretreatment with Y27632, but not by PD98059 (a mitogen-activated protein kinase 1/2 inhibitor) and LY294002 (a phosphatidylinositol 3-kinase inhibitor), indicated that rho-kinase pathway was involved in SPC-induced CTGF expression. Together, these results reveal the potential importance of CTGF induction as a downstream event in SPC-induced cellular responses.
Zhu
Ming Ji
MJ
Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
Kim
Chang Deok
CD
Kwon
Yoo Bin
YB
Kye
Kyung-Chae
KC
Chen
Yuan Yao
YY
Lee
Woong-Hee
WH
Lee
Sangkeun
S
Lim
Jong Soon
JS
Seo
Young-Joon
YJ
Suhr
Ki-Beom
KB
Park
Jang-Kyu
JK
Lee
Jeung-Hoon
JH
D001483:Base Sequence; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor; D018076:DNA, Complementary / Q000235:genetics; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012867:Skin / Q000187:drug effects* / Q000378:metabolism*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
C526317:CCN2 protein, human; D018076:DNA, Complementary; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; C005356:sphingosine phosphorylcholine; D010767:Phosphorylcholine; D055513:Connective Tissue Growth Factor; D013110:Sphingosine