title: Induction of connective tissue growth factor expression by sphingosylphosphorylcholine in cultured human skin fibroblasts.
abstract: 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.
authors.affiliation: Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors.forename: Ming Ji
authors.initials: MJ
authors.lastname: Zhu
authors.forename: Chang Deok
authors.initials: CD
authors.lastname: Kim
authors.forename: Yoo Bin
authors.initials: YB
authors.lastname: Kwon
authors.forename: Kyung-Chae
authors.initials: KC
authors.lastname: Kye
authors.forename: Yuan Yao
authors.initials: YY
authors.lastname: Chen
authors.forename: Woong-Hee
authors.initials: WH
authors.lastname: Lee
authors.forename: Sangkeun
authors.initials: S
authors.lastname: Lee
authors.forename: Jong Soon
authors.initials: JS
authors.lastname: Lim
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Seo
authors.forename: Ki-Beom
authors.initials: KB
authors.lastname: Suhr
authors.forename: Jang-Kyu
authors.initials: JK
authors.lastname: Park
authors.forename: Jeung-Hoon
authors.initials: JH
authors.lastname: Lee
mesh_terms: 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
chemical_list: 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