| Budget Amount *help |
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2012: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
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| Outline of Final Research Achievements |
Aortic dissection (AD) is a frequently fatal medical emergency for which molecular pathogenesis is largely unknown. We examined the role of JAK/STAT signaling in macrophages and vascular smooth muscle cells. In human AD tissue, macrophage infiltration was observed in adventitia and outer layer of the media. STAT3 was strongly activated in macrophages and outer layer of the medial smooth muscle cells. In mouse AD model, activation of JAK/STAT in macrophages promoted proinflammatory M1 differentiation and exacerbated AD progression. Activation of JAK/STAT in smooth muscle cells caused proliferation of adventitial fibroblast, deposition of collagen fibers and reinforcement of the tensile strength of aortic walls, thus preventing AD. In AD model, onset of AD was preceded by the activation of cell cycle, inflammatory response and suppression of smooth muscle cell-specific genes. Our findings indicate that JAK/STAT signaling is activated in AD and plays cell type-specific roles.
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