Investigation for progressive factors of glomerulosclerosis.

肾小球硬化进展因素的调查。

• 批准号: 10470216
• 负责人: DOI Toshio
• 金额: $ 8.26万
• 依托单位: The University of Tokushima (1999)Kyoto University (1998)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10470216/
• 关键词: mesangial cell; transcription factor; glomerulosclerosis; promoter; TGF-β; MSW; 核転送

Glomerulosclerosis is the most important leading to end-stage kidney disease. The mechanism leading to mesangial cell proleferation and phenotypic change is responsible for the subsequent development of glomeruloscierosis. However, the precise mechanism for glomerular injuries is not completely understood. A novel DNA binding protein (MSW) for type IV collagen gene has a multiple functions including large subunit of DNA replication factor C and DNA binding for angiotensinogen and pro-piomelanocortin corticotropin releasing factor. We found that MSW is a transcription factor, which regulates type IV collagen gene and that MSW is a important modulator in a smooth muscle phenotypic change of mesangial cells. The regulation of the gene expression is associated with translocation of MSW from nucleus to cytoplasm. We found that transforming growth factor-β is an important modulator for the translocation of MSW, which eventually regulates the gene expression. These results indicate that MSW protein plays an important role in regulation of smooth muscle phenotype and may contribute to glomerular cell proliferation and the development of glomerulosclerosis.

肾小球硬化是导致终末期肾脏疾病的最重要原因。导致系膜细胞增殖和表型改变的机制是肾小球硬化症的后续发展的原因。然而，肾小球损伤的确切机制尚不完全清楚。一种新型的IV型胶原基因DNA结合蛋白（MSW）具有多种功能，包括大亚基DNA复制因子C和DNA结合血管紧张素原和促黑素促肾上腺皮质激素释放因子。我们发现MSW是调节IV型胶原基因的转录因子，并且MSW是系膜细胞平滑肌表型改变的重要调节剂。基因表达的调控与固体固体废物从细胞核到细胞质的易位有关。我们发现转化生长因子-β是MSW易位的重要调节剂，最终调控该基因的表达。这些结果提示MSW蛋白在平滑肌表型调控中发挥重要作用，可能参与肾小球细胞增殖和肾小球硬化的发生。

项目成果

Mizuno A,Noma Y,Kuwajima M,Murakami T,Zhu M,Shima K.: "Changes in islet capillary angioarchitecture coincide with impaired B-cell function but not with insulin resistance in male Otsuka Long-Evans-Tokushima fatty rats:Dimorphism of the phenotype at on adv

Mizuno A、Noma Y、Kuwajima M、Murakami T、Zhu M、Shima K.：“雄性 Otsuka Long-Evans-Tokushima 脂肪大鼠的胰岛毛细血管结构的变化与 B 细胞功能受损一致，但与胰岛素抵抗无关：

H. Abe, N. lehara, M. Utsunomiya, T. Kita, T. Doi.: "A vitamin D analog regulates mesangial cell smooth muscle phenotypes in a TGF-β type II receptor-mediated manner"J Biol Chem. 274. 20874-20878 (1999)

H. Abe、N. lehara、M. Utsunomiya、T. Kita、T. Doi.：“维生素 D 类似物以 TGF-β II 型受体介导的方式调节系膜细胞平滑肌表型”J Biol Chem 274。 20874-20878 (1999)

Abe H,Ichara N,Utsunomiya M,Kita T,Doi T: "A Vitamin D analog regulates mesangial cell smooth muscle phenotypes in a TGF-β type II receptor-mediated manner"J.Biol.Chem. 274. 20874-20878 (1999)

Abe H、Ichara N、Utsunomiya M、Kita T、Doi T：“维生素 D 类似物以 TGF-β II 型受体介导的方式调节系膜细胞平滑肌表型”J.Biol.Chem. 274. 20874-20878 ( 1999）

Kuwajima M,Horiuchi M,Harashima H,Luk,Hayashi M,Sei M,Kubo T,Komido H,Ono A,Saheki T,Shima K.: "Cardiomegaly in the jyvenile visceral steatosis(JVS)mouse is reduced with acute elevation of heart short-chain acyl-carnitine level after L-cartnitine injectio

Kuwajima M、Horiuchi M、Harashima H、Luk、Hayashi M、Sei M、Kubo T、Komido H、Ono A、Saheki T、Shima K.：“幼年内脏脂肪变性 (JVS) 小鼠的心脏肿大随着急性升高而减少

H. Takeoka, N. Lehara, M. Yanagita, H. Abe, M. Sunamoto, Y. Yamada, T. Kita, T. Doi.: "A multiple transcription factor regulates the smooth muscle phenotype in mesangial cells."Biochem Biophys Res Commun. 252. 290-295 (1998)

H. Takeoka、N. Lehara、M. Yanagita、H. Abe、M. Sunamoto、Y. Yamada、T. Kita、T. Doi.：“多种转录因子调节系膜细胞中的平滑肌表型。”Biochem Biophys