| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Outline of Final Research Achievements |
To obtain a better understanding of the role of HAI-1 in maintaining epidermal integrity, we performed ultrastructural analysis of Hai-1-deficient mouse epidermis and organotypic culture of an HAI-1 knockdown (KD) human keratinocyte cell line, HaCaT. We found that the aggregation of tonofilaments to desmosomes was significantly reduced in Hai-1-deficient mouse with decreased desmosome number. Similar findings were observed in HAI-1 KD HaCaT organotypic cultures. Immunohistochemical analyses demonstrated that p38 was activated in Hai-1-deficient keratinocytes. Silencing of protease-activated receptor-2 (PAR-2) abrogated the activation of p38 in HAI-1 KD HaCaT cells. Furthermore, treatment of HAI-1 KD HaCaT cells by p38 inhibitor abrogated the morphological abnormalities in the organotypic culture. These results suggest that HAI-1 have a critical role in maintaining normal keratinocyte morphology through regulation of PAR-2-dependent p38 MAP kinase signaling.
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