Gene expression profiles of human trabecular meshwork cells induced by triamcinolone and dexamethasone
Gene expression profiles of human trabecular meshwork cells induced by triamcinolone and dexamethasone
复制标题
DOI：
10.1167/iovs.07-0414
复制
发表时间：
2008-05-01
影响因子：
4.4
通讯作者：
Pang, Chi Pui
中科院分区：
文献类型：
--
作者：
Fan, Bao Jian;Wang, Dan Yi;Pang, Chi Pui
目的.曲安奈德（TA）和地塞米松（DEX）是常用于眼部炎症的皮质类固醇，但两者均可引起高眼压。在这项研究中，人类小梁网（TM）细胞的差异基因表达谱响应TA与DEX的比较治疗进行了调查。从用TA或DEX处理的培养的人TM细胞中提取总RNA，并用于微阵列基因表达分析。微阵列实验重复三次。差异表达的基因进行了鉴定的经验贝叶斯方法，并确认实时定量PCR。TA（0.1mg/mL）处理导致15个基因上调和12个基因下调，而1 mg/mL TA导致36个基因上调和21个基因下调。这些基因主要与急性期反应、细胞粘附、细胞周期和生长、生长因子、离子结合、代谢、蛋白水解和转录因子等相关。TA和DEX处理均上调MYOC和GAS 1两个基因，下调SENP 1、ZNF 343和SOX 30三个基因。在已知的原发性开角型青光眼（POAG）基因座上定位了MYOC、SOAT 1、CYP 27 A1、SPOCK、SEMA 6A、EGR 1、GAS 1和ATP 10 A等8个差异表达基因。微阵列技术揭示了TA和DEX处理的人TM细胞的差异基因表达谱，以及TA的剂量效应。TA和DEX治疗有几个差异表达的基因，提示导致高眼压的共同机制。在已知的POAG基因座上发现的一些差异表达基因可能是青光眼基因的候选者。
PURPOSE. Triamcinolone acetonide ( TA) and dexamethasone (DEX) are corticosteroids commonly used for ocular inflammation, but both can cause ocular hypertension. In this study, the differential gene expression profile of human trabecular meshwork (TM) cells in response to treatment by TA in comparison with DEX was investigated.METHODS. Total RNA was extracted from cultured human TM cells treated with TA or DEX and used for microarray gene expression analysis. The microarray experiments were repeated three times. Differentially expressed genes were identified by an empiric Bayes approach and confirmed by real-time quantitative PCR.RESULTS. TA (0.1 mg/mL) treatment resulted in 15 genes upregulated and 12 genes downregulated, whereas 1 mg/mL TA resulted in 36 genes upregulated and 21 genes downregulated. These genes were mainly associated with acute- phase response, cell adhesion, cell cycle and growth, growth factor, ion binding, metabolism, proteolysis and transcription factor. Two genes, MYOC and GAS1, were upregulated, and three genes, SENP1, ZNF343, and SOX30, were downregulated by both TA and DEX treatment. Eight differentially expressed genes were located in known primary open-angle glaucoma (POAG) loci, including MYOC, SOAT1, CYP27A1, SPOCK, SEMA6A, EGR1, GAS1, and ATP10A.CONCLUSIONS. Differential gene expression profiles of human TM cells treated by TA and DEX, and a dosage effect by TA, were revealed by microarray technology. TA and DEX treatment shared several differentially expressed genes, suggesting a common mechanism to cause ocular hypertension. Some differentially expressed genes located in the known POAG loci are potential candidates for glaucoma genes.