Lysophosphatidic acid (LPA) 18:1 transcriptional regulation of primary human gingival fibroblasts.
Lysophosphatidic acid (LPA) 18:1 transcriptional regulation of primary human gingival fibroblasts.
复制标题
DOI：
10.1016/j.gdata.2014.10.014
复制
发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Miyamoto T
中科院分区：
文献类型：
--
作者：
Cerutis DR;Weston MD;Ogunleye AO;McVaney TP;Miyamoto T
多效性、生物活性脂质溶血磷脂酸 [(LPA), 1-酰基-sn-甘油-3-磷酸] 在许多系统的生理学和病理生理学中发挥关键的调节作用。它存在于正常体液中，并且在病理学中升高。在体内，“LPA”以不同的分子种类存在，每种分子都具有不同链长和不饱和度的单一脂肪酸，通过酰基、烷基或烯基连接共价连接至甘油主链。这些物种在对各个 LPA 受体 [(LPAR)、LPA1-6] 的亲和力以及与 G 蛋白的偶联方面有所不同。然而，LPA 18:1 一直是并将继续成为报告研究中最常用的物种。 “LPA”的作用在口腔生物学和病理生理学中仍然没有明确的定义。我们的实验室通过体外研究主要人类唾液 LPA 物种 [18:1、18:0 和 16:0] 在人类口腔细胞中的作用，解决了这一知识空白。这包括牙龈成纤维细胞 (GF)，我们的来自多个捐赠者的流式细胞术数据发现它们表达 LPA1-5。我们还报道，从中度至重度牙周炎患者获得的唾液和龈沟液中，这些物质的药理学水平升高了十倍。由于 LPA 调节转录活性的潜力尚未在口腔系统中得到检验，因此本研究使用全人类基因组微阵列分析来检验以下假设：经 LPA 18:1 处理的人类 GF 将显示与其生物学、伤口愈合和炎症反应相关的基因转录物的显着变化。研究发现 LPA 18:1 可显着调节大量复杂的基因，这些基因对这些类别的 GF 生物学和牙周病至关重要。原始数据已存入 NCBI 的 GEO 数据库，记录为 GSE57496。我们在本研究中使用了研究最多的 LPA 物种 (18:1)。对大量基因（稳态和病理生理学）的显着调节对于研究口腔稳态和炎症相关领域的研究人员很有用
The pleiotropic, bioactive lipid lysophosphatidic acid [(LPA), 1-acyl-sn-glycerol-3-phosphate] exerts critical regulatory actions in physiology and pathophysiology in many systems. It is present in normal bodily fluids, and is elevated in pathology. In vivo, “LPA” exists as distinct molecular species, each having a single fatty acid of varying chain length and degree of unsaturation covalently attached to the glycerol backbone via an acyl, alkyl, or alkenyl link. These species differ in affinities for the individual LPA receptors [(LPARs), LPA1-6] and coupling to G proteins. However, LPA 18:1 has been and continues to be the most commonly utilized species in reported studies. The actions of “LPA” remain poorly defined in oral biology and pathophysiology. Our laboratory has addressed this knowledge gap by studying in vitro the actions of the major human salivary LPA species [18:1, 18:0, and 16:0 ] in human oral cells. This includes gingival fibroblasts (GF), which our flow cytometry data from multiple donors found that they express LPA1-5. We have also reported that these species are ten-fold elevated to pharmacologic levels in the saliva and gingival crevicular fluid obtained from patients with moderate–severe periodontitis. As the potential of LPA to regulate transcriptional activity had not been examined in the oral system, this study used whole human genome microarray analysis to test the hypothesis that LPA 18:1-treated human GF would show significant changes in gene transcripts relevant to their biology, wound-healing, and inflammatory responses. LPA 18:1 was found to significantly regulate a large, complex set of genes critical to GF biology in these categories and to periodontal disease. The raw data has been deposited at NCBI's GEO database as record GSE57496. We used the most investigated LPA species (18:1) in this study. Significant regulation of a large number of genes (homeostasis & pathophysiology) Useful for researchers investigating oral homeostasis & inflammation-related areas