2000 Fiscal Year Final Research Report Summary
Analysis of the biological function of vascular smooth muscle cells regulated by fibrinolytic factors
| Project/Area Number |
11670054
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General physiology
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| Research Institution | Department of Physiology, Kinki University School of Medicine |
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Principal Investigator |
MATSUO Osamu Department of Physiology, Kinki University School of Medicine, Professor, 医学部, 教授 (40030879)
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| Co-Investigator(Kenkyū-buntansha) |
OKADA Kiyotaka Department of Physiology, Kinki University School of Medicine, Assistant, 医学部, 助手 (20185432)
UESHIMA Shigeru Department of Physiology, Kinki University School of Medicine, Assistant Professor, 医学部, 助教授 (30193791)
FUKAO Hideharu Department of Physiology, Kinki University School of Medicine, Assistant, 医学部, 助手 (70218874)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Fibrinolytic system / vascular smooth muscle cells / gene targeting mouse / t-PA / u-PA / PAI-1 / u-PAR / carcinoma cells |
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| Research Abstract |
Vascular smooth muscle cells (SMC) were successfully isolated from thoracic aorta of normal and fibrinolytic factor gene deficient mice. The wild-type SMC (WT/SMC) and the four SMC cultures, lacking urokinase-type plasminogen activator (u-PA^<-/->/SMC), tissue-type plasminogen activator (t-PA^<-/->/SMC), type 1 plasminogen activator inhibitor (PAI-1^<-/->/SMC), and u-PA receptor (u-PAR^<-/->/SMC) were employed to analyze their proliferative activities in the presence of mouse melanoma cells (B16). The growth rates of u-PA^<-/->/SMC, t-PA^<-/->/SMC, and PAI-1^<-/->/SMC as well as WT/SMC were not changed when they were co-cultured with B16 (mixed culture and two-chamber culture) in the presence of 10% fetal calf serum (FCS). On the other hand, the FCS-free conditioned medium of confluent B16 promoted the growth of these SMC to the same extent (〜200%) each of which was associated with both increased tyrosine phosphorylation of 77-kDa protein (7.5〜11-fold) and mitogen-activated protein kinase (MAPK) activity (2-fold). In contrast, only the growth of u-PAR^<-/->/SMC was arrested in these co-cultures. The B16 conditioned medium also suppressed the growth of the SMC of which the phosphorylation of 77- kDa protein and MAPK activity were not altered. These results indicate that these SMC were stimulated by B16-derived growth factor-like substance (s) and that the expressions of u-PA, t-PA and PAI-1 were not involved in these events. However, it is suggested that u-PAR plays an important role in the growth mechanism possibly by forming a functional unit with integrins. Thus, one of the biological responses of SMC to carcinoma cells may be the defense by increased growth of cell-mass against the metastatic process of carcinoma cells at the vascular wall.
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