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
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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