Expression and function of fibroblast growth factor-inducible 14 in human corneal myofibroblasts
Expression and function of fibroblast growth factor-inducible 14 in human corneal myofibroblasts
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DOI：
10.1016/j.exer.2009.03.014
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发表时间：
2009-08-01
影响因子：
3.4
通讯作者：
Murakami, Akira
中科院分区：
文献类型：
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作者：
Ebihara, Nobuyuki;Nakayama, Masafumi;Murakami, Akira
成纤维细胞生长因子诱导14 （Fn14）及其配体肿瘤坏死因子样细胞凋亡弱诱导剂（TWEAK）的相互作用在组织伤口愈合中起重要作用。然而，据我们所知，Fn14在角膜肌成纤维细胞中的表达和功能尚未被研究，而Fn14在角膜基质伤口愈合中起着至关重要的作用。在这项研究中，我们研究了Fn14在角膜肌成纤维细胞中的表达和功能。流式细胞术检测Fn14蛋白表达。角膜肌成纤维细胞强烈表达Fn14蛋白，而角化细胞则不表达。tgf - β(1)促进角质细胞向角膜肌成纤维细胞分化，诱导Fn14表达。这些数据表明，角质细胞表型决定了Fn14的表达水平。ELISA法检测角膜肌成纤维细胞上清液中趋化因子和基质金属蛋白酶(1)。TWEAK通过Fn14增加角膜肌成纤维细胞IL-8、MCP-1和RANTES的产生。tgf - β(1)增强了tweak诱导的这些趋化因子的产生。TWEAK还通过Fn14增加角膜肌成纤维细胞MMP-1和-3的产生，而tgf - β(1)抑制了TWEAK对MMP产生的影响。微调诱导角膜肌成纤维细胞nf - κ B和MAP激酶磷酸化。此外，TWEAK部分抑制了tgf - β促进的角质细胞向角膜肌成纤维细胞的分化(1)。这些数据表明Fn14/TWEAK系统可能在角膜肌成纤维细胞伤口愈合中发挥多种作用。在未来，调节TWEAK/Fn14系统可能成为控制角膜创面愈合的新方法。2009爱思唯尔有限公司版权所有。
The interaction of fibroblast growth factor-inducible 14 (Fn14) and, its ligand tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is known to be important in wound healing of tissues. However, to our knowledge, expression and function of Fn14 in corneal myofibroblasts, which have a crucial role in wound healing of corneal stroma, has not been investigated. In this study, we investigated the expression and function of Fn14 in corneal myofibroblasts. Expression of Fn14 protein was assessed by flow cytometry. Corneal myofibroblasts showed strong expression of Fn14 protein, while keratocytes did not. TGF-beta(1) promoted the differentiation of keratocytes into corneal myofibroblasts, and induced Fn14 expression. These data reveal that keratocytes phenotype determines the level of Fn14 expression. ELISA was used to detect chemokines and matrix metalloproteinases in the supernatant of corneal myofibroblasts cultured with or without stimulation by TWEAK and/or TGF-beta(1). TWEAK increased the production of IL-8, MCP-1, and RANTES by corneal myofibroblasts via Fn14. TGF-beta(1) augmented the TWEAK-induced production of these chemokines. TWEAK also increased the production of MMP-1 and -3 by corneal myofibroblasts via Fn14, while TGF-beta(1) inhibited this effect of TWEAK on MMP production. TWEAK-induced phosphorylation of NF-kappa B and MAP kinase in corneal myofibroblasts. Furthermore, TWEAK partially inhibited the differentiation of keratocytes into corneal myofibroblasts promoted by TGF-beta(1). These data suggest that the Fn14/TWEAK system may have several roles in wound healing by corneal myofibroblasts. In the future, modulation of the TWEAK/Fn14 system may become a novel approach for control corneal wound healing. (C) 2009 Elsevier Ltd. All rights reserved.