糖皮质激素的化学结构不同,但类似的糖皮质激素受体效力规范子集共同和独特的基因在人类的小梁网细胞。
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Nehme Lobenhofer EK,斯塔姆WD,爱德曼杰
糖皮质激素的化学结构不同,但类似的糖皮质激素受体效力规范子集共同和独特的基因在人类的小梁网细胞。
BMC医学基因组学。2009年9月10;2。doi: 10.1186 / 1755-8794-2-58。
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19744340 (在PubMed]
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背景:除了他们的证据确凿的眼部治疗效果,糖皮质激素(gc)会导致影响视觉的副作用包括眼部高血压可能通过形态学和生化改变小梁网细胞(TM)。直接在目前的研究中,我们比较了糖皮质激素受体(GR)效力地塞米松(敏捷),肤轻松醋酸酯(FA)和去炎松醋酸酯(TA),检查已知GRalpha和GRβ亚型的表达,并使用基因表达微阵列比较敏捷的影响,英足总,TA在两个主要人类完整的转录组TM细胞系。敏捷方法:GR结合亲和力,FA,助教是衡量读竞争放射性标记GR结合分析。GR-mediated转录活动评估使用GeneBLAzer beta-lactamase报告基因分析。GRalpha和grβ亚型被免疫印迹评估。总RNA提取TM 86年和93年TM细胞治疗1妈妈敏捷,足总或助教24 hr和用于微阵列基因表达分析。微阵列实验重复三次。被罗塞塔解析器确定基因的差异表达基因表达分析系统。结果:GR结合亲和力(IC50)敏捷,FA, TA是5.4,2.0,和1.5 nM,分别。这些值与GR transactivation EC50的3.0,0.7,和1.5 nM敏捷,足总,和助教。 All four GRalpha translational isoforms (A-D) were expressed in TM 86 and TM 93 total cell lysates, however, the C and D isoforms were more highly expressed relative to A and B. All four GRbeta isoforms (A-D) were also detected in TM cells, although GRbeta-D isoform expression was lower compared to that of the A, B, or C isoforms. Microarray analysis revealed 1,968 and 1,150 genes commonly regulated by DEX, FA, and TA in TM 86 and TM 93, respectively. These genes included RGC32, OCA2, ANGPTL7, MYOC, FKBP5, SAA1 and ZBTB16. In addition, each GC specifically regulated a unique set of genes in both TM cell lines. Using Ingenuity Pathway Analysis (IPA) software, analysis of the data from TM 86 cells showed that DEX significantly regulated transcripts associated with RNA post-transcriptional modifications, whereas FA and TA modulated genes involved in lipid metabolism and cell morphology, respectively. In TM 93 cells, DEX significantly regulated genes implicated in histone methylation, whereas FA and TA altered genes associated with cell cycle and cell adhesion, respectively. CONCLUSION: Human trabecular meshwork cells in culture express all known GRalpha and GRbeta translational isoforms, and GCs with similar potency but subtly different chemical structure are capable of regulating common and unique gene subsets and presumably biologic responses in these cells. These GC structure-dependent effects appear to be TM cell-lineage dependent.