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

点击翻译按钮获取中文摘要

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.