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Sphingosine‐1‐Phosphate Induces Contraction of Floating and Stressed Fibroblast‐Populated Collagen Matrices
Author(s) -
Collier Claiborne Lee,
Watterson Kenneth,
Spiegel Sarah
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a605
Subject(s) - fibroblast , myofibroblast , sphingosine 1 phosphate , contraction (grammar) , microbiology and biotechnology , wound healing , chemistry , sphingosine , receptor , biology , biochemistry , endocrinology , medicine , immunology , in vitro , fibrosis
The serum‐borne bioactive lipid sphingosine‐1‐phosphate (S1P) has been shown to induce proliferation, migration, cytoskeletal rearrangements of fibroblasts and contraction of several smooth muscle types. However, the net effect of S1P on fibroblast reorganization and contraction in the wound healing process has not yet been established. In this study, we used fibroblast populated collagen matrices in order to characterize the actions of S1P. The floating collagen matrix assay models the early phases of wound contraction where there is a net influx of fibroblasts into a wounded matrix. The stressed collagen matrix reflects the latter stages of wound repair where myofibroblasts contract bringing about wound closure from the edges of a predominantly stressed environment. We have now found that S1P as an effective contractile agent in both floating and stressed collagen assays. Furthermore, using selective S1P receptor agonists and antagonists, we have shown that the contraction of the stressed matrix is mediated primarily by the S1P 2 receptor. S1P was also able to transform fibroblasts into myofibroblasts, as indicated by increased basal contraction of stressed matrices and the induction of smooth muscle actin that could be blocked by JTE013, a specific S1P 2 antagonist. Our results suggest that S1P may play an important role in wound healing.