UVB-elicited induction of MMP-1 expression in human ocular surface epithelial cells is mediated through the ERKI/2 MAPK-dependent pathway
UVB-elicited induction of MMP-1 expression in human ocular surface epithelial cells is mediated through the ERKI/2 MAPK-dependent pathway
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DOI：
10.1167/iovs.03-0356
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发表时间：
2003-11-01
影响因子：
4.4
通讯作者：
Wakefield, D
中科院分区：
文献类型：
--
作者：
Di Girolamo, N;Coroneo, MT;Wakefield, D
目的.翼状胬肉是常见的、经常复发的眼表病变，其特征在于组织重塑、细胞增殖、血管生成和炎症。暴露于过量太阳辐射的人翼状胬肉的发病率增加表明，紫外线（UV）光可能在这种疾病的发病机制中发挥关键作用。这些研究集中在胶原酶-1（基质金属蛋白酶[MMP]-1）在翼状胬肉和培养的翼状胬肉上皮细胞中的表达，以确定这种蛋白酶的表达是否可以在暴露于UVB后被修改。翼状胬肉、结膜和角膜缘上皮细胞进行传代培养，并暴露于不同量的UVB。收集条件培养基和RNA，通过明胶酶谱法、Western印迹分析、ELISA和RT-PCR进行分析。此外，整个翼状胬肉标本进行照射，以确定分泌MMP-1水平。免疫组化分析显示，增强MMP-1表达翼状胬肉，正好对应于p63阳性上皮细胞。相反，在正常结膜、利姆布斯和角膜中发现MMP-1反应性显著降低。当翼状胬肉上皮细胞暴露于UVB时，观察到MMP-1的剂量和时间依赖性增加，而抑制剂活性无显著调节。MMP-1在照射的正常结膜上皮细胞或翼状胬肉成纤维细胞中不受影响，但在角膜缘上皮细胞中诱导。UVB照射后MMP-1的诱导虽然不是由中间可溶性因子介导的，但参与了细胞外信号调节激酶（ERK）1/2丝裂原活化蛋白激酶（MAPK）的细胞内途径。总的来说，这些数据支持的假设参与的紫外线和基质金属蛋白酶的发展翼状胬肉，并可能有助于设计新的治疗方法，用于治疗和预防翼状胬肉。
PURPOSE. Pterygia are common, frequently recurring ocular surface lesions characterized by tissue remodeling, cellular proliferation, angiogenesis, and inflammation. The increased incidence of pterygia in persons exposed to excessive solar radiation suggests that ultraviolet (UV) light may play a critical role in the pathogenesis of this disease. These investigations were focused on the expression of collagenase-1 (matrix metalloproteinase [MMP]-1) in pterygia and cultured pterygium epithelial cells, to determine whether the expression of this protease could be modified after exposure to UVB.METHODS. Pterygium, conjunctival, and limbal epithelial cells were subcultured and exposed to various amounts of UVB. The conditioned medium and RNA were harvested for analysis by gelatin zymography, Western blot analysis, ELISA, and RT-PCR. Furthermore, whole pterygium specimens were irradiated to determine secreted MMP-1 levels.RESULTS. Immunohistochemical analysis revealed enhanced MMP-1 expression in pterygia that corresponded precisely with p63-positive epithelial cells. In contrast, significantly less MMP-1 reactivity was found in normal conjunctiva, limbus, and cornea. A dose- and time-dependent increase in MMP-1 was observed when pterygium epithelial cells were exposed to UVB with no significant modulation of inhibitor activity. MMP-1 was not affected in irradiated normal conjunctival epithelial cells or in pterygium fibroblasts but was induced in limbal epithelial cells. Although the induction of MMP-1 after UVB was not mediated by an intermediate soluble factor, the extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein kinase (MAPK) intracellular pathway was involved.CONCLUSIONS. Collectively, these data support the hypothesis of the involvement of UV light and MMPs in the development of pterygia and may assist in devising new therapeutic approaches for the treatment and prevention of pterygia.