Role of JAK2 tyrosine kinase in hypertensive vascular hypertrophy

Research Project

Project/Area Number	11670703
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Circulatory organs internal medicine
Research Institution	OSAKA CITY UNIVERSITY MEDICAL SCHOOL
Principal Investigator	NEGORO Nobuo OSAKA CITY UNIVERSITY MEDICAL SCHOOL, RESEARCH ASSOCIATE, 医学部, 助手 (80180701)
Co-Investigator(Kenkyū-buntansha)	OKAMURA Mikio OSAKA CITY UNIVERSITY MEDICAL SCHOOL, ASSISTANT PROFESSOR, 医学部, 講師 (90169144)
Project Period (FY)	1999 – 2000
Project Status	Completed (Fiscal Year 2000)
Budget Amount *help	¥2,100,000 (Direct Cost: ¥2,100,000) Fiscal Year 2000: ¥600,000 (Direct Cost: ¥600,000) Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywords	hypertension / vascular smooth muscle cells / JAK2 / intracellular signals / hypertrophy
Research Abstract	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.