| Co-Investigator(Kenkyū-buntansha) |
ISHII Masao Yokohama City University, School of Medicine, Professor, 医学部, 教授 (90010363)
SHIONOIRI Hiroshi Yokohama City University, School of Medicine, Associate Prof., 医学部, 講師 (20128599)
GOTOH Eiji Yokohama City University, School of Medicine, Associate Prof., 医学部, 助教授 (30153753)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
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| Research Abstract |
Isolated rat aorta cultured in serum-free medium has been reported to undergo a phenotypic shift to a less differentiated, potentially proliferative state. Using this organ culture system, the expression of an immediate early gene, c-fos, and a component of extracellular matrix, fibronectin (FN), in the aortic wall was studied. A strong induction of c-fos mRNA occurred as early as after 10 min incubation with a peak increase at 1 and 6 hours, declining to a baseline level after 48-hour incubation. Expression of FN was dramatically increased after24h incubation. Balloon dilatation did not alter the aortic mRNA levels for c-fos or FN.Inhibition of protein kinase C (PKC) by H7 decreased the c-fos mRNA by 39.5%. In contrast, CV11974, an angiotensin II type 1 receptor antagonist, or HA1004, a protein kinase A inhibitor, when given alone, did not decrease the c-fos mRNA level. However, when H7, CV11974, and HA1004 were given together, the c-fos mRNA level was decreased by 72.0% (n=3). FN was slightly but significantly induced by intraluminal dilatation with a vessel dilator, which was inhibited by a PKC inhibitor. The strong and prolonged expression of c-fos may have occured as a response to vascular injury given to the aortic wall during the dissection procedure. PKC may play a major role in a signal transduction pathway leading to the induction of c-fos and FN in the aortic wall. Multiple stimuli from different signal transduction systems may be additively or synergistically modulationg the expression of aortic c-fos and FN gene.
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