Transcriptional control mechanism for the expression of alpha1 (1) collagen gene in fibrotic skin disorders

纤维化皮肤疾病中α1（1）胶原蛋白基因表达的转录控制机制

• 批准号: 06670889
• 负责人: HATAMOCHI Atsushi
• 金额: $ 1.34万
• 依托单位: Chiba University (1995)Kawasaki Medical School (1994)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06670889/
• 关键词: type l collagen; fibrosis; transcription; TNF-alpha; type Vl collagen; collagenase; cutis laxa; TNF‐α; VI型コラーゲン; cutis laxa; 皮膚線維症; α_1(I)コラーゲン; 遺伝子; DNA結合因子

Although the expression of type I collagen in filbrotic skin diseases is known to be controlled at the transcriptional level, the control mechanism is poorly understood. We have investigated suppression mechanisms of the transcription of human alpha1 (1) collagen gene by tumor necrosis factor-alpha, and found that the transcription is suppressed through elements located between-101 and-97bp, and between-46 and-38bp of alpha1 (1) collagen gene promoter. We also investigated the regulation of type Vl collagen, and we have found that expression of type Vl collagen genes is increased in cutis laxa fiboblasts. Alterd activity of collagen degradation is another possible mechanism of excessive accumulation of collagen in fibrotic skin diseases. We have found that collagenase gene expression in cutis laxa filbroblasts is upregulated by transcriptional activation of the promoter gene through a TPA-responsive element.

虽然I型胶原蛋白在纤维性皮肤病中的表达已知在转录水平上受到控制，但对其控制机制知之甚少。我们研究了肿瘤坏死因子-α对人α 1（1）胶原基因转录的抑制机制，发现α 1（1）胶原基因启动子的-101 ~-97bp和-46 ~-38bp的元件对转录有抑制作用。我们还研究了VI型胶原的调节，并且我们发现VI型胶原基因的表达在皮肤松弛成纤维细胞中增加。胶原降解活性的改变是纤维化皮肤病中胶原过度积聚的另一可能机制。我们发现，启动子基因通过TPA反应元件的转录激活会上调皮肤松弛拉克萨纤维细胞中胶原酶基因的表达。

项目成果

Mori K,Hatamochi A,Ueki H,Olsen A,Jimenez SA: "The transcription of human α1(I)procollagen gene(CoLlAl)is suppressed by tumor hecrosis factor‐α through proximal short promoter gene" Biochem J. (発表予定).

Mori K、Hatamochi A、Ueki H、Olsen A、Jimenez SA：“肿瘤坏死因子-α 通过近端短启动子基因抑制人类 α1(I) 前胶原基因 (CoLlAl) 的转录” Biochem J.（即将提交） ）。

Mori K,Hatamochi A,Ueki H,Olsen A and Jimenez SA: "The transcription of human α1 (I) procollagen gene (COLIA1) is suppressed by tumor necrosis factor-α through proximal short promoter elements" Biochem J. (発表予定).

Mori K、Hatamochi A、Ueki H、Olsen A 和 Jimenez SA：“肿瘤坏死因子-α 通过近端短启动子元件抑制人类 α1 (I) 前胶原基因 (COLIA1) 的转录” Biochem J.（待提交） ）。

Hatamochi A,Arakawa M,MoriK,MoriY,Ueki H,Yoshioka H,: "Incveased expression of typeVI Collagen genes in cutis laxa fibroblasts" J. Dermatol Sci. 11. 97-103 (1996)

Hatamochi A，Arakawa M，MoriK，MoriY，Ueki H，Yoshioka H，：“皮肤松弛成纤维细胞中 VI 型胶原蛋白基因的表达增加”J. Dermatol Sci。

Hatamochi A,Mori K,Arakawa M,Ueki H and Kondo M: "Collagenase gene expression in cutis laxa filbroblasts is upregulated by transcriptional activation of the promoter gene through a TPA-responsive element" J lnvest Dermatol. (in press). (1996)

Hatamochi A、Mori K、Arakawa M、Ueki H 和 Kondo M：“通过 TPA 响应元件转录激活启动子基因，可上调皮肤松弛成纤维细胞中的胶原酶基因表达”J Invest Dermatol。

Hatamotchi A,Arakawa M,Mori K,Mori Y,Ueki H and Yosioka H: "Increased expression of type Vl collagen genes in cutis laxa fibroblasts" J Dermatol Sci.

Hatamotchi A、Arakawa M、Mori K、Mori Y、Ueki H 和 Yosioka H：“皮肤松弛成纤维细胞中 VI 型胶原蛋白基因的表达增加”J Dermatol Sci。