| Budget Amount *help |
¥17,940,000 (Direct Cost: ¥13,800,000、Indirect Cost: ¥4,140,000)
Fiscal Year 2015: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2013: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
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| Outline of Final Research Achievements |
We investigated roles of ADAM8 in blood development and in inflammatory reactions prior to regenerative myogenesis, by which injured myofibers are eliminated to make new one. No evident defects were observed in ADAM8 knockout (KO) mice. We showed that efficient elimination of injured myofibers during regeneration requires ADAM8. Upon cardiotoxin-induced skeletal muscle injury, neutrophils invade into myofibers through the basement membrane and cluster in wild type, but not in ADAM8 KO mice although neutrophils of the latter infiltrate into interstitial tissues similarly to those of wild type mice. Neutrophils lose their adhesiveness to blood vessels after infiltration, which involves an ectodomain shedding of PSGL-1 on their surface. Expression of PSGL-1 on the surface of neutrophils remain higher in ADAM8 KO than in wild type mice, suggesting that ADAM8 mediates the invasion of neutrophils by the removal of their adhesiveness to blood vessels after infiltration into injured muscle.
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