2013 Fiscal Year Final Research Report
Elucidation of the mechanism of DNA degradation during keratinocyte terminal differentiation and analysis of associated factors in diseased skin with parakeratosis
| Project/Area Number |
24791180
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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 | Tokyo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 表皮角化細胞 / カスパーゼ‐14 / メソトリプシン / フィラグリン / 不全角化 |
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| Research Abstract |
Loss of the nucleus is a critical step during keratinocyte terminal differentiation. However, the mechanism of denucleation is still not fully understood. In this study, we showed that at least two pathways are involved in the denucleation process, that is, profilaggrin N-terminal fragment-dependent and caspase-14-mediated CAD-dependent DNA degradation pathways. Epidermal mesotrypsin liberated a 55-kDa N-terminal fragment of profilaggrin (FLG-N) and FLG-N was translocated into the nucleus. These cells became TUNEL positive. On the other hand, caspase-14 caused limited proteolysis of ICAD, followed by accumulation of caspase activated DNase (CAD), resulting in TUNEL-positive nuclei. Both mesotrypsin and caspase-14 were absent in the parakeratotic area of the skin with atopic dermatitis and psoriasis. These results indicate that multiple pathways are likely to be involved in keratinocyte DNA degradation and the maintenance of the barrier function of epidermis.
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