Induction of connective tissue growth factor expression by sphingosylphosphorylcholine in cultured human skin fibroblasts |
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Authors: | Zhu Ming Ji Kim Chang Deok Kwon Yoo Bin Kye Kyung-Chae Chen Yuan Yao Lee Woong-Hee Lee Sangkeun Lim Jong Soon Seo Young-Joon Suhr Ki-Beom Park Jang-Kyu Lee Jeung-Hoon |
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Affiliation: | Department of Dermatology, School of Medicine, Chungnam National University, Daejeon, Korea. |
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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. |
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Keywords: | connective tissue growth factor Rho kinase skin fibroblasts sphingosylphosphorylcholine |
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