Lysophosphatidic Acid signals through specific lysophosphatidic Acid receptor subtypes to control key regenerative responses of human gingival and periodontal ligament fibroblasts
Autor: | Karmel V. Headen, Terrence M. Wilwerding, Timothy P. McVaney, Afolabi O. Ogunleye, D. Roselyn Cerutis, Lawrence C. Parrish, Joju George, Greg A. Perry, John S. Mattson |
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Rok vydání: | 2009 |
Předmět: |
MAPK/ERK pathway
Adult Male medicine.medical_specialty Periodontal Ligament medicine.medical_treatment Blotting Western Gingiva Phosphatidic Acids chemistry.chemical_compound Young Adult Internal medicine Lysophosphatidic acid medicine Humans Regeneration Calcium Signaling Phosphorylation Receptors Lysophosphatidic Acid Protein kinase A Fibroblast Receptor Cells Cultured Fluorescent Dyes Mitogen-Activated Protein Kinase 1 Wound Healing Mitogen-Activated Protein Kinase 3 biology Growth factor Chemotaxis Organothiophosphates Isoxazoles Fibroblasts Cell biology Endocrinology medicine.anatomical_structure chemistry biology.protein Periodontics lipids (amino acids peptides and proteins) Female Signal transduction Lysophospholipids Propionates Platelet-derived growth factor receptor Signal Transduction |
Zdroj: | Journal of periodontology. 80(8) |
ISSN: | 0022-3492 |
Popis: | We showed that the pluripotent platelet growth factor and mediator lysophosphatidic acid (LPA) controls key regenerative responses of human gingival fibroblasts (GFs) and periodontal ligament fibroblasts (PDLFs) and positively modulates their responses to platelet-derived growth factor (PDGF). This study determined which LPA receptor (LPAR) subtype(s) LPA signals through to stimulate mitogenic extracellular signal-regulated kinase (ERK) 1/2 signaling and chemotaxis and to elicit intracellular Ca(2+) increases in GFs and PDLFs because many healing responses are calcium-dependent.Activation of mitogen-activated protein kinase was determined using Western blotting with an antibody to phosphorylated ERK1/2. Migration responses were measured using a microchemotaxis chamber. GF and PDLF intracellular Ca(2+) mobilization responses to multiple LPA species and LPAR subtype-specific agonists were measured by using a cell-permeable fluorescent Ca(2+) indicator dye.LPA stimulated ERK1/2 phosphorylation via LPA(1)(-3). For GFs, LPA(1) preferentially elicited chemotaxis, and LPA(1-3) for PDLFs, as confirmed using subtype-specific agonists. Elevation of intracellular calcium seems to be mediated through LPA(1) and LPA(3), with little, if any, contribution from LPA(2).To the best of our knowledge, this study provides the first evidence that LPA signals through specific LPAR subtypes to stimulate human oral fibroblast regenerative responses. These data, in conjunction with our previous findings showing that LPA modulates GF and PDLF responses to PDGF, suggest that LPA is a factor of emerging importance to oral wound healing. |
Databáze: | OpenAIRE |
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