The role of methyltransferase, Set7/9 in islet inflammation

甲基转移酶 Set7/9 在胰岛炎症中的作用

• 批准号: 23591324
• 负责人: OGIHARA Takeshi
• 金额: $ 3.33万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591324/
• 关键词: Set9; NF-kB; メチル化; 膵β細胞; 炎症; β細胞; iNOS; NK-kB

Set7/9 is an enzyme that methylates lysine 4 on histone 3 (H3K4) to maintain euchromatin architecture. While Set7/9 contributes to the transactivation of beta cell specific genes, Set7/9 also reportedly binds NF-kB, thus regulating inflammatory genes in non-beta cells. Given that inflammation is a component of beta cell dysfunction in diabetes, the aim of this study was to elucidate the role of Set7/9 on proinflammatory cytokine signaling in beta cells. To induce inflammation, mouse insulinoma cells were treated with a cocktail of pro-inflammatory cytokines. Cytokine treatment induced the expression of iNOS, which was attenuated by the Set7/9 knockdown. Set7/9 knockdown attenuated cytokine-induced methylation of H3K4 in the nos2 promoter. Furthermore, cytokine-induced nos2 expression was reduced in isolated islets from set7/9 knockout mice compared to wild type mice. Our findings suggest that Set7/9 contributes to islet nos2 transcription through activating histone modifications.

Set 7/9是甲基化组蛋白3（H3 K4）上的赖氨酸4以维持常染色质结构的酶。虽然Set 7/9有助于β细胞特异性基因的反式激活，但据报道Set 7/9也结合NF-κ B，从而调节非β细胞中的炎症基因。鉴于炎症是糖尿病β细胞功能障碍的一个组成部分，本研究的目的是阐明Set 7/9对β细胞中促炎细胞因子信号传导的作用。为了诱导炎症，用促炎细胞因子的混合物处理小鼠胰岛素瘤细胞。细胞因子处理诱导iNOS的表达，其通过Set 7/9敲低而减弱。Set 7/9敲低减弱了nos 2启动子中的甘氨酸诱导的H3 K4甲基化。此外，与野生型小鼠相比，在来自set 7/9敲除小鼠的分离的胰岛中，精氨酸诱导的nos 2表达降低。我们的研究结果表明，Set 7/9有助于胰岛nos 2转录通过激活组蛋白修饰。

项目成果

Set7/9 regulates cytokine-induced expresson of iNOS in beta-cell through histone modification

Set7/9 通过组蛋白修饰调节细胞因子诱导的 β 细胞中 iNOS 的表达

• 发表时间: 2013
• 作者: Kyoko Kudo-Fujimaki;Takeshi Ogihara;Yoshio Fujitani;Hirotaka Watada
• 通讯作者: Hirotaka Watada

Set7/9 regulates cytokine-induced expression of iNOS in Beta cells through histone modification

Set7/9 通过组蛋白修饰调节细胞因子诱导的 Beta 细胞中 iNOS 的表达

• 发表时间: 2013
• 作者: Kyoko KUDO-FUJIMAKI;Takeshi OGIHARA;Yoshio FUJITANI;Hirotaka WATADA
• 通讯作者: Hirotaka WATADA

Set7/9はiNOS発現制御を介して膵島炎症に関与する

Set7/9 通过调节 iNOS 表达参与胰岛炎症

• 发表时间: 2013
• 作者: 藤巻杏子;荻原健;原朱美;藤谷与士夫;綿田裕孝
• 通讯作者: 綿田裕孝

Set7/9 regulates cytokine-induced expression of iNOS in beta cells through histone modification.

Set7/9 通过组蛋白修饰调节细胞因子诱导的 β 细胞中 iNOS 的表达。

• 发表时间: 2013
• 作者: 藤巻杏子;荻原 健;福中彩子;藤谷与士夫;綿田裕孝
• 通讯作者: 綿田裕孝