2006 Fiscal Year Final Research Report Summary
Differentiation disturbance in keratinocytes lacking the epidermal fatty acid binding protein gene (E-FABP) which is overexpressed in psoriatic lesions.
| Project/Area Number |
17591156
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Tohoku University |
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Principal Investigator |
HASHIMOTO Akira Tohoku University Hospital, Research associate, 病院, 助手 (40396495)
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| 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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| Project Period (FY) |
2005 – 2006
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| Keywords | Skin / Keratinocyte / FABP / Fatty acid / Psoriasis |
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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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[Journal Article] p53 Homologue, p51/p63, Maintains the Immaturity of Keratinocyte Stem Cells by Inhibiting Notch1 Activity.2007
Author(s)
Okuyama R, Ogawa E, Nagoshi H, Yabuki M, Kurihara A, Terui T, Aiba S, Obinata M, Tagami H, Ikawa S.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Altered emotional behavioral responses in mice lacking brain-type fatty acid-binding protein gene.2006
Author(s)
Owada Y, Abdelwahab SA, Kitanaka N, Sakagami H, Takano H, Sugitani Y, Sugawara M, Kawashima H, Kiso Y, Mobarakeh JI, Yanai K, Kaneko K, Sasaki H, Kato H, Saino-Saito S, Matsumoto N, Akaike N, Noda T, Kondo H.
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Journal Title
Eur J Neurosci 24
Pages: 175-179
Description
「研究成果報告書概要(欧文)」より
