2007 Fiscal Year Final Research Report Summary
New therapeutic approach for alopecia areata using siRNA
Project/Area Number |
18591233
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Dermatology
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Research Institution | Kyoto University (2007) Gunma University (2006) |
Principal Investigator |
NAKAMURA Motonobu Kyoto University, Department ofDermatology, Associate Professor (30303837)
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Project Period (FY) |
2006 – 2007
|
Keywords | Alopecia areata / Th1 / siRNA / C3H / HeJ mouse / siRNA |
Research Abstract |
Autoimmune alopecia (alopecia areata) is considered to be triggered by a collapse of immune privilege in hair follicles. Here we confirmed that infiltrating lymphocytes around the hair follicles of alopecia areata were mostly CD4,CCR5 double positive with few CD4,CCR4 double positive cells suggesting a dominant role of Th1 cells in the alopecic lesion. Local injections of interleukin (IL) -4 or neutralizing antibody against interferon (IFN)-γ were effective for alopecia in C3H/HeJ mice, a mouse model for alopecia areata. Semiquantitative RT-PCR assay demonstrated that intralesional injection of IL-4 suppressed the enhanced IFN-γ mRNA expression in the alopecic skin. Furthermore, Th1 transcription factor T-bet small interfering RNA (siRNA) applications conjugated with cationized gelatin repressed the T-bet expression and showed restoring effects on alopecia in C3H/HeJ mice. MHC class I and II molecules expression in the follicular epithelium was diminished by the T-bet siRNA injections, indicating a restoration of immune privilege. Taken together, the new controlled drug delivery system for siRNA conjugated with gelatin can be a novel candidate for promising therapeutic approaches to various human diseases and cancers.
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[Journal Article] p75 neurotrophin receptor-mediated signaling promotes human hair follicle regression (catagen)2006
Author(s)
EMJ., Peters, MG., Stieglitz, C., Liezman, RW., Overall, M., Nakamura, E., Hagen, BF., Klapp, P., Arck, R., Paus
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Journal Title
Am J Pathol 168
Pages: 221-234
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression2006
Author(s)
K., Foitzik, K., Krause, F., Conrad, M., Nakamura, W., Funk, R., Paus
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Journal Title
Am J Pathol 168
Pages: 748-756
Description
「研究成果報告書概要(欧文)」より
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