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Lysophosphatidic acid receptor subtype‐specific regulation of human oral fibroblast healing responses
Author(s) -
Cerutis D. Roselyn,
George JoJu,
Headen Karmel V.,
Brady Stephanie A.,
Schulte Nancy A.,
Toews Myron L.,
Parrish Lawrence C.,
McVaney Timothy P.,
Wilwerding Terry M.,
Mattson John S.
Publication year - 2008
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.22.1_supplement.805.10
Subject(s) - lysophosphatidic acid , mapk/erk pathway , microbiology and biotechnology , calcium in biology , receptor , intracellular , stimulation , wound healing , calcium , chemistry , fibroblast , endocrinology , biology , signal transduction , biochemistry , immunology , in vitro , organic chemistry
Background: LPA 1–5 receptors (LPARs) bind lysophosphatidic acid (LPA), a G protein‐coupled lipid mediator involved in wound healing. We have published that LPA regulates the growth and migration of human gingival (GF) and periodontal ligament (PDLF) fibroblasts, and that they express LPA 1–3 ; however, which of these subtype(s) mediate stimulation of MAPK, elevation of intracellular calcium, or collagen gel contraction is not known. Methods: Serum‐starved cells in 24‐well plates were stimulated with LPA or subtype‐specific agonists [NAEPA (LPA 1 ); FAP‐12 (LPA 2 ); OMPT (LPA 3 )] for 5 min, and activation of p44/p42 MAPK was assessed by SDS‐PAGE and WB. Serum‐starved cells in 96‐well plates were loaded with Fluo‐3 and elevation of intracellular calcium after stimulation with LPA or subtype‐specific agonists was measured using the FlexStation II (Molecular Devices). Cells in collagen gels were stimulated with LPA or subtype‐specific agonists, and gel areas were measured over time using Sorcerer (Optomax). Results: For GF and PDLF, LPA 1–3 agonists stimulate MAPK, but LPA 1 and LPA 3 mediate elevation of intracellular calcium and collagen gel contraction. The responses mediated through LPA 1 and LPA 3 were inhibited by Ki16425, an LPA ⅓ antagonist. Conclusion: LPA signals through different LPAR subtypes to control specific wound healing‐related responses of GF and PDLF. Support: NIH/NIDCR 1 R15 DE016855‐02 (D.R.C).