Ingram Jennifer L, Antao-Menezes Aurita, Turpin Elizabeth A, Wallace Duncan G, Mangum James B, Pluta Linda J, Thomas Russell S, Bonner James C
The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Respir Res. 2007 Apr 25;8(1):34. doi: 10.1186/1465-9921-8-34.
Exposure to vanadium pentoxide (V2O5) is a cause of occupational bronchitis. We evaluated gene expression profiles in cultured human lung fibroblasts exposed to V2O5 in vitro in order to identify candidate genes that could play a role in inflammation, fibrosis, and repair during the pathogenesis of V2O5-induced bronchitis.
Normal human lung fibroblasts were exposed to V2O5 in a time course experiment. Gene expression was measured at various time points over a 24 hr period using the Affymetrix Human Genome U133A 2.0 Array. Selected genes that were significantly changed in the microarray experiment were validated by RT-PCR.
V2O5 altered more than 1,400 genes, of which ~300 were induced while >1,100 genes were suppressed. Gene ontology categories (GO) categories unique to induced genes included inflammatory response and immune response, while GO categories unique to suppressed genes included ubiquitin cycle and cell cycle. A dozen genes were validated by RT-PCR, including growth factors (HBEGF, VEGF, CTGF), chemokines (IL8, CXCL9, CXCL10), oxidative stress response genes (SOD2, PIPOX, OXR1), and DNA-binding proteins (GAS1, STAT1).
Our study identified a variety of genes that could play pivotal roles in inflammation, fibrosis and repair during V2O5-induced bronchitis. The induction of genes that mediate inflammation and immune responses, as well as suppression of genes involved in growth arrest appear to be important to the lung fibrotic reaction to V2O5.
接触五氧化二钒（V2O5）是职业性支气管炎的一个病因。我们评估了体外暴露于V2O5的培养人肺成纤维细胞中的基因表达谱，以确定在V2O5诱导的支气管炎发病机制中可能在炎症、纤维化和修复过程中发挥作用的候选基因。
在时间进程实验中，将正常人肺成纤维细胞暴露于V2O5。使用Affymetrix人类基因组U133A 2.0芯片在24小时内的不同时间点测量基因表达。通过RT-PCR验证在微阵列实验中显著变化的选定基因。
V2O5改变了1400多个基因，其中约300个基因被诱导，而超过1100个基因被抑制。诱导基因特有的基因本体论类别（GO）包括炎症反应和免疫反应，而抑制基因特有的GO类别包括泛素循环和细胞周期。通过RT-PCR验证了十几个基因，包括生长因子（HBEGF、VEGF、CTGF）、趋化因子（IL8、CXCL9、CXCL10）、氧化应激反应基因（SOD2、PIPOX、OXR1）和DNA结合蛋白（GAS1、STAT1）。
我们的研究确定了多种可能在V2O5诱导的支气管炎的炎症、纤维化和修复过程中起关键作用的基因。介导炎症和免疫反应的基因的诱导以及参与生长停滞的基因的抑制似乎对肺对V2O5的纤维化反应很重要。
