| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
We investigated the effect of stabilization of HIF-1α by treatment with dimethyloxalylglycine (DMOG); a prolyl hydroxylase inhibitor on FasL-induced alveolar epithelial apoptosis in vitro and in vivo. DMOG increased HIF-1α protein levels in MLE12 cells, and attenuated FasL-induced caspase activation and cell death. Inhibition of HIF-1 pathway by echinomycin; an inhibitor of HIF-1 binding to DNA, or by siRNA transfection abolished the anti-apoptotic effect of DMOG. Intraperitoneal administration of DMOG also suppressed apoptosis in lung tissues in the mice intratracheally instilled with FasL. Moreover, DMOG attenuated disruption of alveolar barrier and histological changes in these mice. Prolyl hydroxylase inhibition protects lung epithelial cells from FasL-induced apoptosis and attenuated the lung injury.
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