| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
E-NTPD8 was highly expressed in the apical aspect of epithelia cells of the colon. Entpd8-deficent mice showed higher levels of ATP in feces than that in wild-type mice. Entpd8-eifceint mice developed severe colitis during administration of dextran sodium sulfate (DSS). In this context, Entpd8-deficeint mice exhibited increased number of neutrophils in the colonic lamina propria. In addition, Entpd8-deifceint mice suffered from severe colitis-associated colorectal cancer following treatment with azoxymethane plus DSS. Introduction of the P2rx4 deficiency into Entpd8-deficeint mice drastically reduced large intestinal pathology with decreased number of neutrophils during DSS administration. Treatment with ATPgS induced prolonged life span of neutrophils isolated from the colon of wild-type mice, but not P2rx4-deficent mice. These findings demonstrate that E-NTPD8 in intestinal epithelial cells prevents neutrophil-mediated exacerbation of colitis via P2RX4 by hydrolysis of luminal ATP.
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