Lysophosphatidic Acid Signals Through Specific Lysophosphatidic Acid Receptor Subtypes to Control Key Regenerative Responses of Human Gingival and Periodontal Ligament Fibroblasts
Lysophosphatidic Acid Signals Through Specific Lysophosphatidic Acid Receptor Subtypes to Control Key Regenerative Responses of Human Gingival and Periodontal Ligament Fibroblasts
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DOI：
10.1902/jop.2009.080624
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发表时间：
2009-08-01
影响因子：
4.3
通讯作者：
Cerutis, D. Roselyn
中科院分区：
文献类型：
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作者：
George, JoJu;Headen, Karmel V.;Cerutis, D. Roselyn
背景：我们发现多能血小板生长因子和介质溶血磷脂酸（LPA）控制人牙龈成纤维细胞（GF）和牙周膜成纤维细胞（PDLF）的关键再生反应，并积极调节它们对血小板衍生生长因子（PDGF）的反应。本研究确定了 LPA 信号通过哪种 LPA 受体 (LPAR) 亚型来刺激促有丝分裂细胞外信号调节激酶 (ERK) 1/2 信号传导和趋化性，并引发细胞内 GF 和 PDLF 中 Ca2+ 的增加，因为许多愈合反应是钙依赖性的。方法：使用磷酸化 ERK1/2 抗体，使用蛋白质印迹法测定丝裂原激活蛋白激酶的激活。使用微趋化室测量迁移反应。使用细胞可渗透的荧光 Ca2+ 指示剂染料测量 GF 和 PDLF 对多种 LPA 种类和 LPAR 亚型特异性激动剂的细胞内 Ca2+ 动员反应。结果：LPA 通过 LPA(1-3) 刺激 ERK1/2 磷酸化。对于 GF，LPA(1) 优先引发趋化性，而 LPA(1-3) 对于 PDLF 优先引发趋化性，正如使用亚型特异性激动剂所证实的那样。细胞内钙的升高似乎是通过 LPA(1) 和 LPA(3) 介导的，而 LPA(2) 的贡献很小（如果有的话）。结论：据我们所知，这项研究提供了第一个证据，表明 LPA 通过特定 LPAR 亚型发出信号来刺激人类口腔成纤维细胞再生反应。这些数据与我们之前的研究结果相结合，表明 LPA 调节 GF 和 PDLF 对 PDGF 的反应，表明 LPA 是口腔伤口愈合中一个新兴的重要因素。牙周病杂志 2009；80：1338-1347。
Background: 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 Ca2+ increases in GFs and PDLFs because many healing responses are calcium-dependent.Methods: 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 Ca2+ mobilization responses to multiple LPA species and LPAR subtype-specific agonists were measured by using a cell-permeable fluorescent Ca2+ indicator dye.Results: 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).Conclusions: 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. J Periodontol 2009;80:1338-1347.