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家鼠紫外线辐射诱导的碱性成纤维细胞生长因子(bFGF)的光复活作用及其在角膜病变形成中的作用

Photoreactivation of ultraviolet radiation-induced basic fibroblast growth factor (bFGF) and the role of bFGF in corneal lesion formation in Monodelphis domestica.

作者信息

Ley R D, Miska K B, Kusewitt D F

机构信息

Department of Cell Biology and Physiology and the Cancer Research and Treatment Center, University of New Mexico, Albuquerque, New Mexico 87131, USA.

出版信息

Environ Mol Mutagen. 2001;38(2-3):175-9. doi: 10.1002/em.1069.

Abstract

Chronic ultraviolet radiation (UVR) exposure to the eyes of Monodelphis domestica causes corneal opacification, neovascularization, and fibrosarcoma induction. By immunohistochemistry and Western blotting, we have shown that one to four exposures of the eyes of this opossum to UVR enhances basic fibroblast growth factor (bFGF) expression by the corneal epithelium. Treatment with photoreactivating light, which selectively removes UVR-induced pyrimidine dimers, suppresses bFGF induction, indicating that UVR induction of bFGF is ultimately due to DNA damage. Furthermore, UVR-induced corneal tumors derived from corneal keratocytes express bFGF mRNA and protein, as determined by immunohistochemistry and in situ hybridization. Taken together, these findings suggest that bFGF acts in both an autocrine and a paracrine manner to stimulate corneal fibroplasia, neovascularization, and tumor development.

摘要

长期暴露于紫外线(UVR)下会导致家短尾负鼠眼睛出现角膜混浊、新生血管形成和纤维肉瘤。通过免疫组织化学和蛋白质印迹法,我们发现,让这种负鼠的眼睛接受一至四次紫外线照射后,角膜上皮细胞的碱性成纤维细胞生长因子(bFGF)表达会增强。用能选择性去除紫外线诱导的嘧啶二聚体的光复活光进行处理,可抑制bFGF的诱导,这表明紫外线诱导bFGF最终是由于DNA损伤。此外,通过免疫组织化学和原位杂交确定,源自角膜角膜细胞的紫外线诱导角膜肿瘤表达bFGF mRNA和蛋白质。综上所述,这些发现表明,bFGF以自分泌和旁分泌方式发挥作用,刺激角膜纤维增生、新生血管形成和肿瘤发展。

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