Analysis of transcriptional control mechanism for the expression of type I collagen in fibrotic skin disorders
| Project/Area Number |
17591183
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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 | Dokkyo Medical University |
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Principal Investigator |
HATAMOCHI Atsushi Dokkyo Medical University, 医学部, Professor (90172923)
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| Co-Investigator(Kenkyū-buntansha) |
OKITA Hiroshi Dokkyo medical University, 医学部, Associate Professor (20360076)
YAMAZAKI Soji Dokkyo medical University, 医学部, Professor (80008333)
SOUTOME Akihiro Dokkyo medical University, 医学部, Assistant (30383003)
HORIE Masaki Dokkyo medical University, 医学部, Assistant (30360077)
安田 真一 獨協医科大学, 医学部, 助手 (60133279)
川村 由美 獨協医科大学, 医学部, 助手 (50337383)
酒井 司 獨協医科大学, 医学部, 助手 (80215590)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥2,710,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | type I collagen gene expression / transcription / fibroblasts / systemic sclerosis / Erythromycin analog EM703 / EM201 / I型コラーゲン / 遺伝子発現 / エリスロマイシン誘導体 / EM703 / マクロライド |
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| Research Abstract |
Fibrotic skin diseases such as systemic sclerosis (SSc) are characterized by excessive accumulation of collagen in the skin and a variety of internal organs. The accumulation of collagen is thought to result from enhanced transcription of collagen in fibroblasts. Collagen type I, a most abundant protein in the dermis, consists of two α1 (I) chain and one α2 (I) chain which are coordinately expressed. None of treatment modalities for patients with SSc has brought satisfactory improvement. We would like to present effects of the Erythromycin analog EM703 and EM201 on collagen transcription in normal and scleroderma fibroblasts. We found that EM703 reduced collagen production and the mRNA levels of α1 (I) collagen in a dose-dependent manner in the normal fibroblasts. The transcription of COL1A1 was downregulated as detected by the luciferase assay. The downregulation was also detected using DNA containing various short lengths of the COL1A1 promoter region. EM703 did not inhibit COL1A1 transcription when the luciferase assay was performed using DNA containing the COL1A1 promoter with a short substitution mutation of the CCAAT box. Decreased production of type I collagen at the transcriptional level was also found in SSc fibroblasts treated with EM703. These results suggest that EM703 inhibits the transcription of type I collagen in both normal and SSc fibroblasts, and that the transcription is inhibited through the CCAAT box of the COL1A1 promoter. On the other hand EM201 induced collagen production and the mRNA levels of type I collagen in a dose-dependent manner in both normal and SSc fibroblasts.
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Report
(4 results)
Research Products
(10 results)
