Molecular basis of proliferative diseases associated with BMP receptor mutations

与 BMP 受体突变相关的增殖性疾病的分子基础

• 批准号: 22390059
• 负责人: BEPPU Hideyuki
• 金额: $ 8.07万
• 依托单位: University of Toyama
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390059/
• 关键词: 大腸ポリープ; 上皮間質相互作用; BMP; 受容体; 遺伝子改変マウス; 癌

BMP signaling is transduced by BMP receptors （e.g., BMPR2), which are located at cell membrane. Mutations of BMP receptor genes are known to cause pulmonary hypertension, congenital heart defects, and juvenile polyposis syndrome. We investigated molecular mechanism, by which BMP receptor mutations develop ccell-proliferative diseases, using BMPR2-deficient mice and fibroblast cells isolated from the mice. We found that BMPR2-deficient fibroblast cells promoted proliferation of epithelial cells. Also, suppression of BMP signaling augmented TNF-induced NK-kB activation. These results suggest that increased inflammatory response may play an important role in the pathogenesis of the diseases caused by the BMP receptor mutations

BMP信号传导由BMP受体（例如，BMPR 2），它们位于细胞膜上。已知BMP受体基因的突变会导致肺动脉高压、先天性心脏缺陷和青少年息肉病综合征。我们使用BMPR 2缺陷小鼠和从小鼠中分离的成纤维细胞研究BMP受体突变发展成细胞增殖性疾病的分子机制。我们发现BMPR 2缺陷的成纤维细胞促进上皮细胞的增殖。此外，BMP信号传导的抑制增强了TNF诱导的NK-kB激活。这些结果表明，炎症反应的增加可能在BMP受体突变引起的疾病的发病机制中起重要作用

项目成果

Aberrant Calcium/Calmodulin-Dependent Protein Kinase II (CaMKII) Activity Is Associated with Abnormal Dendritic Spine Morphology in the ATRX Mutant Mouse Brain

• DOI: 10.1523/jneurosci.4816-10.2011
• 发表时间: 2011-01-05
• 期刊: JOURNAL OF NEUROSCIENCE
• 影响因子: 5.3
• 作者: Shioda, Norifumi;Beppu, Hideyuki;Fukunaga, Kohji
• 通讯作者: Fukunaga, Kohji

Augmented NF-kB signaling in BMPR2 deficient cells as the model for juvenile polyposis syndrome

BMPR2 缺陷细胞中增强的 NF-kB 信号传导作为幼年息肉病综合征的模型

• 发表时间: 2012
• 作者: 高島康郎;鈴木淳史;秀和泉 神垣真由美 関貴弘 酒井規雄;Masami Yamada;Beppu H
• 通讯作者: Beppu H

BMPR2-deficient fibroblast cells promote proliferation of epithelial cells in a cell culture system

BMPR2缺陷的成纤维细胞促进细胞培养系统中上皮细胞的增殖

• 发表时间: 2011
• 作者: Inoue;K.;et al.;沢村達也;Otsuka M;Beppu H
• 通讯作者: Beppu H

Basolateral BMP signaling in polarized epithelial cells.

• DOI: 10.1371/journal.pone.0062659
• 发表时间: 2013
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Saitoh M;Shirakihara T;Fukasawa A;Horiguchi K;Sakamoto K;Sugiya H;Beppu H;Fujita Y;Morita I;Miyazono K;Miyazawa K
• 通讯作者: Miyazawa K

BMPシグナル伝達異常と疾患との関わり(総説)

BMP信号异常与疾病的关系（综述）

• 发表时间: 2012
• 期刊: 臨床化学
• 作者: Fukuda;A.;et al.;別府秀幸
• 通讯作者: 別府秀幸