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Signaling Events During Induction of Plasminogen Activator Inhibitor-1 Expression by Sphingosylphosphorylcholine in Cultured Human Dermal Fibroblasts.
- Source :
-
Journal of Investigative Dermatology . Jun2004, Vol. 122 Issue 6, p1365-1371. 7p. - Publication Year :
- 2004
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Abstract
- Sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid metabolite that can enhance wound healing. In a search for effectors downstream of SPC in the wound-healing process, we found that the expression of the gene for plasminogen activator inhibitor-1 (PAI-1) was significantly affected. ELISA and western blot analyses showed that SPC markedly induced PAI-1 production in human dermal fibroblasts cultured in vitro. Inhibition by pre-treatment with pertussis toxin (PTx), but not by tyrphostin A47 (a receptor tyrosine kinase inhibitor), indicated that PTx-sensitive G proteins were involved in SPC-induced PAI-1 expression. SPC elicited a rapid and transient increase in intracellular calcium levels ([Ca2+]i), measured using laser scanning confocal microscopy, which was partly mediated through PTx-sensitive G proteins. Pre-treatment with thapsigargin, but not with EGTA, abolished SPC-induced PAI-1 expression, indicating the importance of Ca2+ release from internal stores. Phorbol-12-myristate-13-acetate (PMA) induced the expression of PAI-1, and pre-treatment with Ro 31-8220 (a PKC inhibitor) markedly suppressed SPC-induced PAI-1 expression. SPC-induced PAI-1 expression was also significantly suppressed by PD98059 (a specific MAPK kinase 1/2 inhibitor). Consistent with this result, SPC stimulated the phosphorylation of p42/44 extracellular signal-regulated kinase (ERK). Together, these results suggest that SPC induces PAI-1 production through a G protein-coupled calcium increase and downstream kinase signaling events in cultured human dermal fibroblasts. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0022202X
- Volume :
- 122
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Journal of Investigative Dermatology
- Publication Type :
- Academic Journal
- Accession number :
- 13219424
- Full Text :
- https://doi.org/10.1111/j.0022-202X.2004.22615.x