Microarray analysis of the rat lacrimal gland following the loss of parasympathetic control of secretion
Microarray analysis of the rat lacrimal gland following the loss of parasympathetic control of secretion
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DOI：
10.1152/physiolgenomics.00011.2004
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发表时间：
2004-06-17
影响因子：
4.6
通讯作者：
Beuerman, RW
中科院分区：
文献类型：
--
作者：
Nguyen, DH;Toshida, H;Beuerman, RW
以往的研究表明，毒蕈碱副交感神经输入到泪腺（LG）的损失导致泪液分泌的急剧减少和LG结构的深刻变化。在这项研究中，我们使用DNA微阵列来研究的基因表达的基因的分泌功能和组织的LG。Long-Evans大鼠麻醉氯胺酮/甲苯噻嗪（80：10毫克/公斤）的混合物进行单侧切片的岩浅大神经，翼腭神经节的输入。7天后，测量泪液分泌，处死动物，通过光学显微镜检查LG的结构变化。使用U34 A基因芯片将来自对照和实验LG（n = 5）的总RNA用于DNA微阵列分析。使用三种统计算法（检测、变化调用和信号对数比），使用微阵列套件（5.0）和数据挖掘工具（3.0）确定差异基因表达。泪液分泌显著减少，所有实验眼均出现角膜溃疡。光学显微镜下显示的LG. DNA微阵列分析显示，与内质网和高尔基体，包括参与蛋白质折叠和加工的基因下调的腺泡结构的故障。相反，转录细胞骨架和细胞外基质成分，炎症和细胞凋亡上调。显著上调基因的数量（116）显著大于下调基因的数量（49）。去除大鼠LG的主要分泌输入导致与严重干眼症相关的临床症状。分泌途径的组分受到负面影响，并且细胞增殖和炎症的增加可能导致副交感神经切除泪腺中组织的丧失。
Previous studies showed that loss of muscarinic parasympathetic input to the lacrimal gland (LG) leads to a dramatic reduction in tear secretion and profound changes to LG structure. In this study, we used DNA microarrays to examine the regulation of the gene expression of the genes for secretory function and organization of the LG. Long-Evans rats anesthetized with a mixture of ketamine/xylazine (80:10 mg/kg) underwent unilateral sectioning of the greater superficial petrosal nerve, the input to the pterygopalatine ganglion. After 7 days, tear secretion was measured, the animals were killed, and structural changes in the LG were examined by light microscopy. Total RNA from control and experimental LGs (n = 5) was used for DNA microarray analysis employing the U34A GeneChip. Three statistical algorithms (detection, change call, and signal log ratio) were used to determine differential gene expression using the Microarray Suite (5.0) and Data Mining Tools (3.0). Tear secretion was significantly reduced and corneal ulcers developed in all experimental eyes. Light microscopy showed breakdown of the acinar structure of the LG. DNA microarray analysis showed downregulation of genes associated with the endoplasmic reticulum and Golgi, including genes involved in protein folding and processing. Conversely, transcripts for cytoskeleton and extracellular matrix components, inflammation, and apoptosis were upregulated. The number of significantly upregulated genes ( 116) was substantially greater than the number of downregulated genes ( 49). Removal of the main secretory input to the rat LG resulted in clinical symptoms associated with severe dry eye. Components of the secretory pathway were negatively affected, and the increase in cell proliferation and inflammation may lead to loss of organization in the parasympathectomized lacrimal gland.