The disturbed feed forward transcriptional regulation mechanism coupled with disturbed intracellular lipid metabolism in keratinocytes of congenital ichthyosis model mice
| Project/Area Number |
25670502
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Dermatology
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| Research Institution | Nagoya University |
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Principal Investigator |
OGAWA Yasushi 名古屋大学, 医学部附属病院, 助教 (10567754)
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| Co-Investigator(Renkei-kenkyūsha) |
SUGIURA Kazumitsu 名古屋大学, 大学院医学系研究科, 准教授 (70335032)
AKIYAMA Masashi 名古屋大学, 大学院医学系研究科, 教授 (60222551)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | 皮膚科学 / 先天性角化異常症 / 道化師様魚鱗癬 / NLSDI / ケラチノサイト / 脂質代謝 / 転写調節 / エピジェネティクス / PPAR |
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| Outline of Final Research Achievements |
This study was designed to verify the hypothesized feed forward mechanism of lipid metabolism-transcriptional regulation in differentiating keratinocytes, and find possible application of this putative mechanism in the treatment of congenital skin diseases. For this purpose we utilized Abca12-deficient as a mouse model of harlequin ichthyosis and CGI-58-deficient mouse as a model of neutral lipid storage disease with ichthyosis. Primary keratinocytes taken from the skin of model mice were treated with agonists of PPAR family nuclear receptors. A PPARγagonist restored the decreased expression of a keratinocyte differentiation marker. It could not, however, provide an overall reversal of the disease phenotype. An attempt to inject of PPAR agonist in utero failed to rescue the early death of newborn mice. Search for skin-specific triglyceride lipase was performed using siRNA targeted at PNPLA family members suggested the putative lipase exists otherwise.
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Report
(3 results)
Research Products
(5 results)
