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

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).

Entering, Linked with the Sphinx: Lysophosphatidic Acids Everywhere, All at Once, in the Oral System and Cancer

“…We determined by flow cytometry that human GF and PDLF express at least LPA1-LPA5 [ 34 ]. Their expression of so many LPAR subtypes supports and leads to the inescapable conclusion that LPA is a critical mediator necessary for these cells’ functions and that the actions of LPA must be exerted via at least these first five of the six cloned LPARs.…”

“…Seminal in vitro work from our group [ 31 , 32 ] established that LPA is a key regulatory factor for primary human gingival and periodontal ligament fibroblasts (GF and PDLF) and, thus, for oral biology. We then showed that LPA positively regulates their wound-healing and regenerative responses [ 33 ] by signaling mainly through LPA1 and LPA3, which these fibroblasts express at high levels, and that they also express at least five (LPA1-LPA5) of the six cloned LPA receptors (LPARs) [ 34 ]. LPA1 appears to be the most active in LPA signaling [ 35 ].…”