Deletion of Cflip in the epidermis results in TNFR1-dependent and independent lethal dermatitis
| Project/Area Number |
26893265
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Dermatology
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| Research Institution | Toho University |
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Principal Investigator |
PIAO Xuehua 東邦大学, 医学部, 博士研究員 (70739812)
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| Project Period (FY) |
2014-08-29 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 皮膚炎 / 細胞死 / apoptosis / ケラチノサイト / cFLIP / バリア機能 / 皮膚の分化 / TNF / ケラチノサイトの分化 |
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| Outline of Final Research Achievements |
Cellular FLICE-inhibitory protein (cFLIP) is a protease-inactivate caspase 8 homologue that binds to caspase 8 and blocks apoptosis. Recent studies have shown that cFLIP prevents TNFα-induced apoptosis of keratinocytes by using inducible keratinocyte-specific Cflip-deficient mice (Weinlich et al., Cell Rep. 2013; Panayotova-Domitrova et al., Cell Rep. 2013). However, it is unclear whether TNFα-independent pathway might contribute to keratinocyte apoptosis in Cflip-deficient mice. Here we show that epidermis-specific Cflip-deficient mice (CflipE-KO) die in utero. Intriguingly, CflipE-KO;Tnfr1-/- mice were born at the expected Mendelian ratio, but still developed severe dermatitis soon after birth. Enhanced apoptosis and a defect in differentiation of keratinocytes were observed inCflipE-KO;Tnfr1-/- mice. Together, cFLIP plays a crucial role in protection of keratinocytes from TNFR1-dependent and -independent apoptosis.
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Report
(3 results)
Research Products
(5 results)
