Investigation of the roles of Smad linker region phosphoryulation in epithelial-mesenchymal transition and tissue fibrosis.

研究 Smad 连接区磷酸化在上皮间质转化和组织纤维化中的作用。

• 批准号: 19592036
• 负责人: SAIKA Shizuya
• 金额: $ 2.66万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19592036/
• 关键词: 水晶体上皮細胞; 網膜色素上皮細胞; 線維芽細胞; トランスフォーミング成長因子; Smad; リン酸化; 上皮-間葉系移行; 線維化; 増殖硝子体網膜症; マウス; 水晶体外傷; aTN4マウス水晶体細胞; 免疫組織化学; 水晶体上被細胞; 網膜色素被細胞; 繊維芽細胞; 繊維化; ミドルリンカー領域; ウエスタンブロット; シグナル伝達

In cultures of retinal pigment epithelial cell line, ARPE-19 and mouse lens epithelial cell line, a-TN4, TGFbeta1 addition activates phosphorylation of Smad2/3 C-terminal and middle rinker region along with epithelial-mesenchymal transition (EMT). Phorphorylation of Smad2/3 middle lilnker was observed even under TGFbeta1-minus condition and seemed to be attenuated with inhibitors of MAPKs. Immunohistochemistry of human samples showed that EMT-lens cells exhibited phosphorylation of Smad3 middle renker region more prominently as compared with its C-terminus phosphrylation. C-terminus phosphorylation was not observed in smooth muscle action-positive cells. Rat lens injury experiments suggested that invlovement of JNK and p38 in Smad middle linker region phosphorylation. EMT-related gene expression was overall detecterd in mosue proliferative vitreoretinopathy (PVR) model. Immunohistochemistry showed both C-terminus and middle linker region phosphorylations of Smad3. Adenoviral overexpression of dominant negative p38 seemed to suppress middle linker region phosphorylation of Smad3. Investigations on human samples and its animal model, as well as cell culture experiments, suggetsed involvement of Smad3 middle linker region phosphorylation in EMT-related fibrogenic ocular pathologies.

在视网膜色素上皮细胞系、ARPE-19细胞系和小鼠晶状体上皮细胞系的培养中，α-TN4、TGFbeta1的加入激活了Smad2/3 C末端和中间Rinker区的磷酸化，并伴随着上皮-间充质转化(EMT)。即使在TGFbeta1缺失的情况下，Smad2/3中间体的磷酸化也被观察到，并且似乎被MAPKs的抑制剂所减弱。免疫组织化学结果显示，EMT晶状体细胞Smad3中间肾区的磷酸化程度明显高于其C末端的磷酸化程度。在平滑肌肌动阳性细胞中未观察到C末端的磷酸化。大鼠晶状体损伤实验表明，JNK和p38参与了Smad中间连接区的磷酸化。在苔藓增殖性玻璃体视网膜病变(PVR)模型中全面检测EMT相关基因的表达。免疫组织化学显示Smad3的C末端和中间连接区均有磷酸化。腺病毒过表达显性阴性p38似乎抑制了Smad3的中间连接区的磷酸化。对人类样本及其动物模型的研究以及细胞培养实验表明，SMAD3中间连接区的磷酸化参与了EMT相关的眼部纤维化的病理过程。

项目成果

白内障手術合併症の基礎と臨床.

白内障手术的基本和临床并发症。

• 发表时间: 2009
• 作者: 久高久美子;行徳雄二;小篠史郎;谷原秀信;雑賀司珠也;雑賀司珠也
• 通讯作者: 雑賀司珠也

Extracellular Matrix Componnents, Osteopontin and Tenascin C, Modulate Smad Signal and Attenuate Epithelial-mesenchymal Transition In Vivo.

细胞外基质成分、骨桥蛋白和腱蛋白 C 可调节 Smad 信号并减弱体内上皮间质转化。

• 发表时间: 2008
• 作者: Shizuya Saika;Susan R. Rittling;David T. Denhardt;Chia-Yang Liu;Winston Kao
• 通讯作者: Winston Kao

Epithelial-mesenchymal transition as a therapeutic target for prevention of ocular tissue fibrosis

• DOI: 10.2174/187153008783928343
• 发表时间: 2008-03-01
• 期刊: Endocrine Metabolic & Immune Disorders-Drug Targets
• 影响因子: 1.9
• 作者: Saika, Shizuya;Yamanaka, Osamu;Ikeda, Kazuo
• 通讯作者: Ikeda, Kazuo

Gelatin particle agglutination (PA) antibody: comparison to neutralizing antibody (NT) and hemagglutination inhibition (HI) antibody and relationship to IgG avidity.

明胶颗粒凝集 (PA) 抗体：与中和抗体 (NT) 和血凝抑制 (HI) 抗体的比较以及与 IgG 亲合力的关系。

• 发表时间: 2008
• 期刊: Kansenshogaku Zasshi. 82
• 作者: Saika S;Matsunaga T;Ogawa T;Ichinohe S.
• 通讯作者: Ichinohe S.

繊維化疾患の治療標的としてのEMT

EMT作为纤维化疾病的治疗靶点

• 发表时间: 2009
• 作者: 久高久美子;行徳雄二;小篠史郎;谷原秀信;雑賀司珠也;雑賀司珠也;雑賀司珠也;雑賀司珠也;雑賀司珠也
• 通讯作者: 雑賀司珠也