Transcriptional control mechanism for the expression of type I collagen gene in fibrotic skin disorders and related diseases
| Project/Area Number |
08670948
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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 | Chiba University |
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Principal Investigator |
HATAMOCHI Atsushi Chiba University School of Medicine, Associate Professor, 医学部, 助教授 (90172923)
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| Co-Investigator(Kenkyū-buntansha) |
KURODA Kei Chiba University School of Medicine Assistant, 医学部, 助手 (90225300)
TSUKIFUJI Reiko Chiba University School of Medicine Hospital Lecturer, 医学部・付属病院, 講師 (70218048)
SHINKAI Hiroshi Chiba University School of Medicine Professor, 医学部, 教授 (90030957)
坂井 靖夫 千葉大学, 医学部・附属病院, 助手 (50272315)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1996: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | type I collagen / promoter gene / Pur alpha / Pur beta / TGF beta / TGF beta receptor / transcription / Purα / Purβ / TGFβ / TGFβレセプター / 遺伝子発現 / TNF-α / COLF1 / 皮膚線維症 |
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| Research Abstract |
Collagen type I,a most abundant protein in the dermis, consists of two alphal(I) chain and one alpha2(I) chain which are coordinately expressed. ColFl, a DNA binding protein which specifically binds to a segment of the alpha2(I)collagen promoter at -400bp upstream of the start of transcription, activates transcription of the alpha2(I)collagen gene in vitro. We investigated on the partial sequences of polypeptide and the cDNA cloning of this transcriptional factor of the alpha2(I)collagen gene. The protein purified by sequence-specific DNA affinity chromatography were found to consist of 42kDa and 40.5 kDa polypeptides. Sequences of peptide fragments from 42kDa polypeptide were identical to Pur alpha, is a nuclear protein which has been reported to binds to a upstream region of human c-myc gene. Some of those from 40kDa polypeptide were identical to Pur beta, has been partially sequenced and has regions of strong homology to Pur alpha Full length of Pur beta cDNA were sequenced. The deductive amino acid sequences of Pur alpha and Pur beta showed 61.4% homology. Previous studies have demonstrated that the expression of type I collagen, the most abundant protein in the dermis, is reduced in in vitro aging fibroblast cultures, but the mechanism controlling the reduction of type I collagen expression is not understood. We found that the mRNA levels of alphal(I) collagen, TGFbeta, and TGFbeta receptors I and II in late-passage fibroblasts were reduced, and the TGF beta receptor binding in late-passage fibroblasts was lower than that in early-passage fibroblasts.
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Report
(3 results)
Research Products
(5 results)
