| Project/Area Number |
23791302
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Dermatology
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 皮膚炎症 / 再生学 / ナイアシン / ペラグラ / 紫外線 / 光線過敏症 |
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| Research Abstract |
Pellagra is a photosensitivity syndrome characterized by three “D’s”: diarrhea, dermatitis and dementia as a result of niacin deficiency. However, the molecular mechanisms of photosensitivity dermatitis underlying the hallmark abnormalities of this syndrome are unclear. Here we show that enhanced photosensitivity in mice was induced by treatment with a niacin antagonist as well as niacin-deficient diets, and that severe diarrhea with weight loss was induced by treatment with the niacin ntagonist, which suggest that this is a model of pellagra. Intriguingly, the niacin antagonist induced elevated expression of COX-2 and PGE syntheses (Ptges) mRNAs. The niacin antagonist treatment-induced photosensitivity was alleviated by a COX inhibitor, deficiency of Ptges, or blockade of EP4 receptor signaling. In line with the above findings in mice, analysis of skin lesions of pellagra patients confirmed the enhanced expression of Ptges. Taken together, these findings indicate that niacin deficiency results in the development of photosensitivity in pellagra mediated by signaling through EP4 in response to increased PGE production.
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