Role of JAK2 tyrosine kinase in hypertensive vascular hypertrophy

JAK2酪氨酸激酶在高血压血管肥大中的作用

• 批准号: 11670703
• 负责人: NEGORO Nobuo
• 金额: $ 1.34万
• 依托单位: OSAKA CITY UNIVERSITY MEDICAL SCHOOL
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670703/
• 关键词: hypertension; vascular smooth muscle cells; JAK2; intracellular signals; hypertrophy

Role of JAK2 in hypertrophy of vascular smooth muscle cells in vitro and in vivo.1) JAK2 inhibitor, AG-490, inhibited hypertophy (cell size, 3H-thimidine uptake and 3H-leucine uptake) in cultured vascular smooth muscle cells induced by angiotensin II (AII).2) AG-490 inhibited tyrosine phosphorylation of epidermal growth factor (EGF) receptors in AII-induced vascular hypertrophy in cultured vascular smooth muscle cells.3) AG-490 inhibited vascular hyperophy (weight) of thoracic aortas from 12-week-old spon-taneously hypertensive rats (SHRs) in vivo.4) AG-490 also inhibited tyrosine phophorylation of EGF receptors from media of thoracic aortas in 15-week-old SHRs. However, AG-490 did not changed blood pressure in the rats.5) AG-490 inhibited interferon stimulated response element (IRSE), interon gamma-activation site (SAS), and sis-inducible element (SIE), which were detected by the gel shift assays.These results suggest that JAK2 involves in the vascular hypertrophy of hypertensive rats, possbly through cross-talk of EGF receptors in vitro and in vivo.

JAK 2在体内外血管平滑肌细胞肥大中的作用：1）JAK 2抑制剂AG-490抑制血管平滑肌细胞肥大，（小区大小，AG-490抑制血管紧张素II（AII）诱导的血管平滑肌细胞表皮生长因子（EGF）受体酪氨酸磷酸化。3）AG-490在体内抑制12周龄自发性高血压大鼠（SHR）胸主动脉的血管肥厚（重量）; 4）AG-490在体内抑制12周龄自发性高血压大鼠（SHR）胸主动脉的血管肥厚（重量）。490还抑制15周龄SHR胸主动脉中EGF受体的酪氨酸磷酸化。AG-490对高血压大鼠的血压无明显影响。5）凝胶迁移实验显示，AG-490抑制干扰素刺激的反应元件（IRSE）、干扰素γ激活位点（SAS）和信号转导诱导元件（SIE），提示JAK 2可能通过与EGF受体的体内外交互作用参与高血压大鼠血管肥厚的发生。