Lysophosphatidic acid (LPA) receptor subtypes on human gingival and periodontal ligament fibroblasts are regulated by PDGF

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Abstract
LPA is a pleiotropic G protein‐coupled lipid mediator involved in many homeostatic and patho‐physiologic aspects of cellular regulation. It binds to LPA1‐6 receptor (LPAR ) subtypes. It is co‐released by activated platelets together with platelet‐derived growth factor (PDGF). We have published that human gingival (GF) and periodontal ligament (PDLF) fibroblasts express LPA1‐3, and that LPA positively regulates their responses to PDGF. In this study, we tested the hypotheses that 1) LPA binds to additional LPAR subtypes on GF and PDLF and 2) PDGF regulates plasma membrane expression of LPARs. Using immunohistochemistry (IHC) with LPAR subtype‐specific antibodies (Abs) we probed for LPA1‐5. Determination of cell‐surface expression of LPARs was done by flow cytometry (FC) with these Abs. Cells were grown in 100‐mm dishes and serum‐starved prior to measuring LPARs by FC. We found that GF and PDLF also express LPA4 and LPA5. PDGF‐BB at10 ng/ml modulated the cell‐surface expression of several LPARs between 2 and 6h post‐treatment. From these results, we conclude that 1) multiple LPAR subtypes modulate the responses of GF and PDLF to LPA, and 2) PDGF‐BB exerts complex regulation of LPARs in these cells. Support: NIH/NIDCR 1 R15 DE016855‐03 (D.R.C).