Particle radiation alters expression of matrix metalloproteases resulting in ECM remodeling in human lens cells
Particle radiation alters expression of matrix metalloproteases resulting in ECM remodeling in human lens cells
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DOI：
10.1007/s00411-006-0087-7
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发表时间：
2007-06-01
影响因子：
1.7
通讯作者：
Blakely, E. A.
中科院分区：
文献类型：
--
作者：
Chang, P. Y.;Bjornstad, K. A.;Blakely, E. A.
相对较低剂量的空间辐射与太空旅行者白内障发病率增加和早期出现有关。透镜是人体对辐射敏感的器官，有一个非常明显的辐射损伤晚期终点--白内障。然而，许多分子变化发生在透镜辐射曝光后不久，并在出现混浊之前很久。我们研究的目标是阐明与粒子辐射诱导的白内障发生相关的早期机制，最终目标是制定对策。在Lawrence Berkeley National Lab（LBNL）或Brookhaven National Lab的NASA空间辐射实验室（NSRL），将正常培养的非永生化人透镜细胞培养在基质包被的塑料组织培养容器中，并用粒子束进行辐照。在辐射暴露后的不同时间收获样品。使用集中的遗传方法，从对照和辐照样品的总RNA和蛋白质提取物进行处理，并探测与细胞外基质（ECM）蛋白酶相关的基因的表达。基质金属蛋白酶（MMP）以前已经在成人死后人晶状体、白内障后眼内透镜（IOL）手术囊袋和永生化人透镜细胞培养物中进行了研究。这些不同模型系统的表达模式存在显着差异。我们有证据表明，在透镜纤维分化过程中MMP家族基因的细胞阶段特异性表达，以及辐射诱导的MMP表达失调的改变。我们的数据表明，辐射暴露可能会导致辐射应激反应的表达差异，这可能会影响选择性ECM重塑和细胞分化。
Relatively low doses of space radiation have been correlated with an increased incidence and earlier appearance of cataracts in space travelers. The lens is a radiosensitive organ of the body with a very obvious late end point of radiation damage-cataract. However, many molecular changes occur in the lens soon after radiation exposure and long before the appearance of an opacification. The goal of our research is to elucidate early mechanisms associated with particle radiation-induced cataractogenesis, with the ultimate goal of developing countermeasures. Normal, cultured non-immortalized human lens cells were grown on matrix-coated plastic tissue culture vessels and irradiated with particle beams at Lawrence Berkeley National Lab (LBNL) or at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Lab. Samples were harvested at different times after radiation exposure. Using a focused genetic approach, total RNA and protein extracts from control and irradiated samples were processed and probed for the expression of genes associated with extracellular matrix (ECM) proteases. Matrix metalloproteinases (MMPs) have previously been studied in adult postmortem human lenses, in post-cataract intraocular lens (IOL) surgery capsular bags and with immortalized human lens cell cultures. Significant differences exist in the expression pattern with these various model systems. We have evidence for the cell stage-specific expression of MMP family of genes during lens fiber differentiation, and for radiation-induced alterations in the misregulation of MMP expression. Our data indicate that radiation exposure may lead to differences in the expression of radiation stress responses, which may impact selective ECM remodeling and cell differentiation.