Investigation on the role of FGF-1 in CCN2 gene regulation and osteoarthritis

FGF-1在CCN2基因调控与骨关节炎中的作用研究

• 批准号: 18J10073
• 负责人: El Seoudi Abdellati
• 金额: $ 1.09万
• 依托单位: Okayama University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2018
• 资助国家: 日本
• 起止时间: 2018-04-25 至 2020-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18J10073/
• 关键词: osteoarthritis; FGF-1; CCN2; Osteoarthritis; Chondrocytes

FGF-1 strongly inhibits the gene expression of CCN2, which regenerates cartilage, whereas it enhances its own gene expression in chondrocytes. This effect is thought to be critical in osteoarthritis development mediated by FGF-1. In order to find out an intracellular factor that mediate this gene regulation, I initially analyzed chromatin immunoprecipitation (ChIP) sequencing data downloaded from the ENCODE database. According to the ChIP data, both CCN2 and FGF-1 genes contains 2 regions accompanied by H3K4me2, which is a hallmark of promoter, enhancer and silencer, in the proximal promoter area. Interestingly, I found a transcription factor that binds to one of these 2 regions of both genes. Gene expression of this transcription factor was confirmed in human chondrocytic cells. After silencing the expression of this factor in those cells by siRNAs, I evaluated the effect of FGF-1 on the CCN2 and FGF-1 genes. As expected, FGF-1 failed to regulate the CCN2 and FGF-1 genes after the silencing of the transcription factor gene. These results indicate that this single transcription factor mediates both CCN2 repression and auto-induction by FGF-1. Utility of a molecule that inhibits the function of this transcription factor in osteoarthritis treatment is suggested herein.

FGF-1强烈抑制再生软骨的CCN2基因表达，同时增强其自身在软骨细胞中的基因表达。这种作用被认为是由FGF-1介导的骨关节炎发展的关键。为了找出介导这种基因调控的细胞内因子，我首先分析了从ENCODE数据库下载的染色质免疫沉淀（ChIP）测序数据。ChIP数据显示，CCN2和FGF-1基因在近端启动子区均含有2个伴随H3K4me2的区域，H3K4me2是启动子、增强子和沉默子的标志。有趣的是，我发现了一个转录因子与这两个基因的两个区域中的一个结合。在人软骨细胞中证实了该转录因子的基因表达。在sirna沉默这些细胞中该因子的表达后，我评估了FGF-1对CCN2和FGF-1基因的影响。正如预期的那样，在转录因子基因沉默后，FGF-1无法调控CCN2和FGF-1基因。这些结果表明，该单一转录因子介导CCN2抑制和FGF-1的自动诱导。本文建议在骨关节炎治疗中使用抑制该转录因子功能的分子。

项目成果

Roles of MMP3 in cargo signature and transmissive activity of cancer extracellular vesicles and in tumorigenesis.

MMP3 在癌症细胞外囊泡的货物特征和传输活性以及肿瘤发生中的作用。

• 发表时间: 2019
• 作者: エマン・タハ;江口傑徳;奥舎有加;十川 千春;アブデラティフ・エルソウディ;久保田聡;佐藤あやの;岡元邦彰
• 通讯作者: 岡元邦彰

Effect of Fibroblast growth factor 1 (FGF-1) on connective tissue growth factor (CCN2/CTGF) gene expression in chondrocytic cells and its possible role in osteoarthritis

成纤维细胞生长因子 1 (FGF-1) 对软骨细胞中结缔组织生长因子 (CCN2/CTGF) 基因表达的影响及其在骨关节炎中的可能作用

• 发表时间: 2018
• 作者: El-Seoudi A;Abd El Kader T;Nishida T;Aoyama E;Eguch T;Takigawa M;Kubota S
• 通讯作者: Kubota S

Roles of MMP3-containing extracellular vesicles in tumorigenesis, CD9-exosome release and cell-cell communication in cancer

含有 MMP3 的细胞外囊泡在癌症发生、CD9 外泌体释放和细胞间通讯中的作用

• 发表时间: 2019
• 作者: Eman A. Taha;Yuka Okusha;Chiharu Sogawa;Abdellatif El-Seoudi;Satoshi Kubota;Ayano Satoh;Kuniaki Okamoto;Taka Eguchi
• 通讯作者: Taka Eguchi

軟骨細胞におけるCCN3遺伝子の糖代謝を介した制御

通过葡萄糖代谢调节软骨细胞中的CCN3基因

• 发表时间: 2018
• 作者: 明石 翔;西田 崇;El-Seoudi A;滝川正春;飯田征二;久保田聡
• 通讯作者: 久保田聡

Effects of Fibroblast Growth Factor 1 (FGF-1) on CCN2 Gene Expression in Chondrocytic Cells

成纤维细胞生长因子 1 (FGF-1) 对软骨细胞 CCN2 基因表达的影响

• 发表时间: 2019
• 作者: Abdellatif Elseoudi;Tarek Abd ElKader;Takashi Nishida;Takanori Eguchi;Eriko Aoyama;Takako Hattori;Masaharu Takigawa;Satoshi Kubota
• 通讯作者: Satoshi Kubota