Pathomechanism of cerebral small vessel induced by TGFβ1 signalling

TGFβ1信号诱导脑小血管的病理机制

• 批准号: 22591595
• 负责人: MIZUNO Toshiki
• 金额: $ 2.91万
• 依托单位: Kyoto Prefectural University of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-22591595/
• 关键词: TGF β; 脳小血管病変; 高血圧モデルラット; TGFβ; 脳小血管病; 脳腎連関

CARASIL is caused by the mutation n the serine protease HTRA1, which regulates transforming growth factor-β (TGF-beta 1) signaling. The pathological feature of CARASIL is arteriosclerosis with intimal thickening and dense collagen fibers, loss of vascular smooth-muscle cells, and hyaline degeneration of the tunica media in cerebral small arteries, which resembles nonhereditary cerebral small-vessel disease. While TGF-beta 1 plays a key role in the maintenance of normal blood vessel wall structure, the contribution of TGF-beta to the development of atherosclerosis is obscure. We examined TGF-beta 1 in rat removing unilateral kidney and overloading deoxycorticosterone（DOCA）and salt to clarify a role of TGF-beta 1 in the hypertensive brain and kidney. After unilateral kidney was removed, DOCA and 1% NaCl were administrated to a rat for 3 or4 weeks（DOCA-salt）. Systolic blood pressure (SBP) and heart rates (HR) in the rat were measured once a week by tail cuff method. After measuring mean arterial blood pressure (MAP) and HR by a cannula from inguinal artery invasively, kidney, aorta, cerebral artery and brain were removed. TGF -beta 1 in each organ was measured by ELISA and western blotting.SBP and MAP in the rat with DOCA-salt significantly increased during the course. TGF bera1 increased from 0.06 ± 0.005 ng/mg to 0.16 ± 0.012 ng/mg in the kidney, from 0.59 ± 0.07 ng/mg to 2.64 ± 0.45 ng/mg in the aorta after 3 weeks. While TGF bera1 did not change significantly from 0.019 ± 0.004 ng/mg to 0.022 ± 0.003 ng/mg after 3 weeks, but it increased significantly after 4 weeks in the cervical artery and the brain.The increase of the TGF bera1 in the kidney and the aorta precedes the increase of the TGF bera1 in the cervical artery and the brain.

CARASIL 是由丝氨酸蛋白酶 HTRA1 突变引起的，该酶调节转化生长因子-β (TGF-β 1) 信号传导。 CARASIL的病理特征是动脉硬化，内膜增厚，胶原纤维致密，血管平滑肌细胞缺失，脑小动脉中膜透明变性，类似于非遗传性脑小血管病。虽然 TGF-β1 在维持正常血管壁结构中发挥着关键作用，但 TGF-β 对动脉粥样硬化发展的贡献尚不清楚。我们在切除单侧肾脏并超负荷脱氧皮质酮（DOCA）和盐的大鼠中检测了TGF-β1，以阐明TGF-β1在高血压脑和肾脏中的作用。摘除大鼠单侧肾脏后，给予DOCA和1% NaCl（DOCA-盐）3或4周。采用尾套法每周测量一次大鼠收缩压（SBP）和心率（HR）。通过腹股沟动脉插管侵入性测量平均动脉血压（MAP）和HR后，切除肾、主动脉、脑动脉和大脑。通过ELISA和蛋白质印迹法测定各器官中的TGF-β1。DOCA-盐治疗期间大鼠的SBP和MAP显着升高。 3周后，肾脏中的TGF bera1从0.06±0.005ng/mg增加到0.16±0.012ng/mg，主动脉中从0.59±0.07ng/mg增加到2.64±0.45ng/mg。而3周后TGF bera1从0.019±0.004 ng/mg到0.022±0.003 ng/mg没有显着变化，但4周后颈动脉和大脑中TGF bera1显着增加。肾脏和主动脉中TGF bera1的增加先于颈动脉和大脑中TGF bera1的增加。

项目成果

深部白質病変進行のリスク因子としてのTGF-B1値の検討

检查 TGF-B1 水平作为深部白质病变进展的危险因素

• 发表时间: 2010
• 作者: 栗山長門、水野敏樹;ら
• 通讯作者: ら

深部白質病変進行のリスク因子としてのTGF-β1 値の検討

检查 TGF-β1 水平作为深部白质病变进展的危险因素

• 发表时间: 2010
• 作者: 栗山 長門; 水野 敏樹;笠井 高士;田邑 愛子;渡邉 明子;山田 恵;渡邊 能行;中川 正法
• 通讯作者: 中川 正法

高血圧モデルラットにおける TGFβ1 発現

高血压模型大鼠TGFβ1的表达

• 发表时间: 2011
• 作者: 水野敏樹;王佳虹;鳥羽裕恵;中野亜里沙;東條千里;野田和揮;小原幸;中川正法;中田徹男
• 通讯作者: 中田徹男

高血圧モデルラットにおけるTGFβ1発現

高血压模型大鼠TGFβ1的表达

• 发表时间: 2011
• 作者: 水野敏樹;ら
• 通讯作者: ら

認知症と血管性要因

痴呆与血管因素

• 发表时间: 2010
• 期刊: 老年期認知症研究会誌
• 作者: N. Kuriyama;T. Mizuno;Y. Ohshima;K. Yamada;E. Ozaki;M. Shigeta;S. Mitani;M. Kondo;S. Matsumoto;K. Takeda;M. Nakagawa;Y. Watanabe;中川正法,水野敏樹
• 通讯作者: 中川正法,水野敏樹