Epidermal growth factor receptor signaling is partially responsible for the increased matrix metalloproteinase-1 expression in ocular epithelial cells after UVB radiation
Epidermal growth factor receptor signaling is partially responsible for the increased matrix metalloproteinase-1 expression in ocular epithelial cells after UVB radiation
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DOI：
10.1016/s0002-9440(10)62992-6
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发表时间：
2005-08-01
影响因子：
6
通讯作者：
Wakefield, D
中科院分区：
文献类型：
--
作者：
Di Girolamo, N;Coroneo, M;Wakefield, D
翼状胬肉是人类眼表的炎性、侵袭性和增殖性病变，其中基质金属蛋白酶（MMP）胶原酶-1（MMP-1）高度表达。翼状胬肉的发展可能涉及MMP-1活性对间质纤维胶原，丰富的细胞外基质成分的角膜，其诱导紫外线（UVB）。我们研究了负责增强MMP-1的表达在翼状胬肉上皮细胞UVB暴露和/或治疗后的有丝分裂原活化蛋白激酶或表皮生长因子受体的化学抑制剂的途径。UVB对MMP-1的诱导作用与肝素结合表皮生长因子样生长因子和表皮生长因子介导的MMP-1的诱导作用相当。表皮生长因子受体抑制剂PD 153035部分阻断UVB介导的MMP-1的诱导，并完全废除其生产后的刺激与肝素结合的表皮生长因子样生长因子或表皮生长因子。UVB暴露增强磷酸化形式的ERK 1/2在一个时间依赖性的方式，而ERK 1/2抑制剂PD 98059减少这种诱导至少五倍。c-jun和c-fos的转录本早在UVB暴露后2小时就被检测到，并且被PD 98059抑制。一个特定的细胞内信号通路负责增强生产的关键酶，变性完整的纤维胶原蛋白的识别有重要意义的病理生理学和未来的治疗翼状胬肉。
Pterygia are inflammatory, invasive, and proliferative lesions of the human ocular surface in which the matrix metalloproteinase (MMP) collagenase-1 (MMP-1) is highly expressed. Pterygia development may involve MMP-1 activity against interstitial fibrillar collagen, an abundant extracellular matrix component of the cornea, and its induction by ultraviolet light (UVB). We examined the pathways responsible for enhanced expression of MMP-1 in pterygium epithelial cells after UVB exposure and/or treatment with chemical inhibitors of mitogen-activated protein kinases or epidermal growth factor receptor. The induction of MMP-1 by UVB was comparable to that mediated by heparin-binding epidermal growth factor-like growth factor and epidermal growth factor. The epidermal growth factor receptor inhibitor PD153035 partially blocked the UVB-mediated induction of MMP-1 and totally abrogated its production after stimulation with either heparin-binding epidermal growth factor-like growth factor or epidermal growth factor. UVB exposure enhanced the phosphorylated form of ERK1/2 in a time-dependent manner whereas the ERK1/2 inhibitor PD98059 decreased this induction by at least fivefold. Transcripts for c-jun and c-fos were detected as early as 2 hours after UVB exposure and were suppressed by PD98059. The identification of a specific intracellular signaling pathway responsible for the enhanced production of a key enzyme that denatures intact fibrillar collagen has important implications for understanding the pathophysiology and future therapy for pterygia.