The Role of c-Jun N-terminal Kinases 1/2 in Transforming Growth Factor β1-induced Expression of Connective Tissue Growth Factor and Scar Formation in the Cornea
The Role of c-Jun N-terminal Kinases 1/2 in Transforming Growth Factor β1-induced Expression of Connective Tissue Growth Factor and Scar Formation in the Cornea
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DOI：
10.1177/147323000903700316
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发表时间：
2009-05-01
影响因子：
1.6
通讯作者：
Wu, X-Y
中科院分区：
文献类型：
--
作者：
Chang, Y.;Wu, X-Y
转化生长因子β (1) （tgf - β(1)）在结缔组织生长因子（CTGF）介导的角膜瘢痕形成中起重要作用。本研究旨在探讨c-Jun n -末端激酶（JNK） 1和2对端粒酶永生人角膜基质成纤维细胞（THSF）中tgf - β(1)调控的CTGF基因表达和角膜瘢痕形成的影响。采用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑（MTT）法研究CTGF、tgf - β(1)和一种INK抑制剂（SP600125）对THSF细胞增殖的影响。CTGF和tgf - β(1)均能促进THSF细胞增殖，而SP600125抑制这一作用。免疫荧光分析显示，tgf - β(1)刺激JNK1/2的激活，诱导细胞迁移，SP600125抑制了这一作用。实时逆转录-聚合酶链反应分析显示，SP600125预处理可降低创面和角膜瘢痕形成组织中CTGF、纤维连接蛋白和胶原I α(1)基因mRNA水平。
Transforming growth factor beta(1), (TGF-beta(1)) plays an important role in corneal scar formation, mediated by connective tissue growth factor (CTGF). This study was designed to investigate the effect of c-Jun N-terminal kinase (JNK) 1 and 2 on TGF-beta(1)-regulated CTGF gene expression and corneal scar formation in telomerase-immortalized human corneal stroma fibroblast (THSF) cells. The effects of CTGF, TGF-beta(1) and a INK inhibitor (SP600125) on the proliferation of THSF cells were studied using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Both CTGF and TGF-beta(1) increased THSF cell proliferation and SP600125 inhibited this effect. immunofluorescence analysis showed that TGF-beta(1) stimulated the activation of JNK1/2 and induced cell migration, effects that were inhibited by SP600125. Analysis by real-time reverse transcription-polymerase chain reaction showed that the mRNA levels of the genes for CTGF, fibronectin and collagen I alpha(1) in wound and corneal scar formation were reduced by SP600125 pre-treatment.