| Co-Investigator(Kenkyū-buntansha) |
OKUYAMA Ryuhei Tohoku University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (80292332)
OWADA Yuji Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (20292211)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2005: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
Fatty acid binding proteins (FABP) is postulated to serve as a lipid shuttle, solubilizing hydrophobic fatty acids and delivering them to the appropriate intracytoplasmic sites. Among FABP consisting of at least 13 isoforms, keratinocytes only express epidermal-type FABP (E-FABP) which is overexpressed in actively proliferating states like psoriasis and healing wounds. We analyzed functions of E-FABP using E-FABP null keratinocytes. Our examinations revealed decreased amount of fatty acids, especially of linoleic acid, in the E-FABP null epidermis. Although no difference in the growth of the E-FABP null keratinocytes with that of wild cells, the null keratinocytes showed decrease of induction of differentiation specific proteins (keratin 1 and involcrin). Linoleic acid did not modulate the keratinocyte differentiation directly, but linoleic acid derivatives, hydroxyoctadecadienoic acid (HODE), induced the differentiation specific proteins. Moreover, HODE activated NF-kB signal pathway which promoted keratinocyte differentiation. The activity of NF-kB pathway was decreased in the E-FABP null keratinocytes, which supported the idea that the decreased linoleic acid connects disturbed differentiation via the derivatives of linoleic acid. On the other hand, peroxisome proliferator activated receptor (PPAR) pathway, which had been reported as main target of E-FABP, did not show any difference in the E-FABP null keratinocytes. From our results, E-FABP affects NF-kB pathway through fatty acid metabolism, which may connect E-FABP overexpression with pathomechanism in psoriasis because NF-kB plays important roles in cell survival and differentiation.
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