2009 Fiscal Year Final Research Report
What is the mechanism of the accelerated migration of epiplakin-deficient keratinocytes?
| Project/Area Number |
20790807
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Dermatology
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| Research Institution | Oita University |
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Principal Investigator |
GOTO Mizuki Oita University, 医学部, 助教 (70433050)
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| Project Period (FY) |
2008 – 2009
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| Keywords | エピプラキン、 / 自己抗原、 / 自己免疫性水疱症、 / 表皮細胞、 / ケラチン、 / 創傷治癒 |
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| Research Abstract |
Epiplakin (EPPK) belongs to the plakin family of cytolinker proteins, and like other plakin family proteins, BPAG1 (an autoantigen of bullous pemphigoid), and plectin, in vitro experiments have demonstrated that EPPK plakin repeat domains (PRD) and/or linker region binds to intermediate filaments. Elimination of EPPK by gene targeting in mice resulted in acceleration of keratinocytes migration during wound healing. EPPK expressed in proliferating keratinocytes at the wound edges, and from its putative function of keratin binding, it was supposed that the disturbance of keratin network of EPPK-null mice during wound stages. In order to confirm this hypothesis and to know the precise localization of EPPK related to keratin filaments, we compared the non-wound epidermis and the wound epidermis of wild-type and EPPK-/-mice. Non-wound epidermis and the wound epidermis of wild-type and EPPK-/-mice were examined by immunofluorescence and electron microscopy after double immunostaining. EPPK presented more with keratin 10(K10) in the non-wound epidermis. Although the expression of keratin 5(K5), K10 and keratin 6(K6) were not altered in EPPK deficient mice during wound stage, diameter of keratin filaments decreased in EPPK deficient keratinocytes. Immunoelecron microscopic study revealed that EPPK colocalized with K5,K10 and K6 at the wound stage. This data indicated that EPPK accelerates keratin bundling in proliferating keratinocytes during wound stage and EPPK may contribute to reinforce keratin network under stressful environment.
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