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首页> 外文期刊>Matrix biology: Journal of the International Society for Matrix Biology >Col1a2 enhancer regulates collagen activity during development and in adult tissue repair.
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Col1a2 enhancer regulates collagen activity during development and in adult tissue repair.

机译：Col1a2增强剂可调节发育过程中和成人组织修复过程中的胶原蛋白活性。

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摘要

An enhancer region in the type I collagen alpha 2 chain (pro-Col1a2) promoter has been previously identified approximately -17 kb away from the transcription start site. This upstream region termed the far-upstream-enhancer contains three DNAse I hypersensitive sites and has been shown to be conserved between mouse and human genes. In this study, we used transgenic mice harbouring the complete promotor sequence of the pro-Col1a2 gene up to -17 kb to examine the role of this enhancer in the expression and regulation of the collagen gene during development and in adult tissues pre and post injury. By careful histological mapping of the collagen type I endogenous gene distribution with that of the transgene driven by the mouse far upstream enhancer, we are able to show that in early days of collagen expression, E8.5-9.5, the endogenous gene preceded transgene expression. However, by E11.5 the overall pattern becomes synchronous with a few exceptions. In adult tissue, both endogenous and transgene expression are attenuated and both are reactivated in parallel in various organs by physical injury or fibrogenic cytokine injection. These findings suggest that the enhancer is central to the activation of the collagen type I and that mice harbouring this enhancer/reporter provide a useful model to follow collagen gene transcription activity and for investigating cellular activity in tissue fibrosis.
机译：I型胶原蛋白α2链（pro-Col1a2）启动子中的增强子区域先前已在距转录起始位点约-17 kb处鉴定出来。被称为远上游增强子的该上游区域包含三个DNAse I超敏位点，并且已经显示在小鼠和人类基因之间是保守的。在这项研究中，我们使用了具有高达-17 kb的pro-Col1a2基因完整启动子序列的转基因小鼠，研究了这种增强子在发育过程中以及损伤前后成年组织中胶原基因表达和调控中的作用。 。通过仔细的组织学I型胶原内源性基因分布与小鼠远上游增强子驱动的转基因的组织学映射，我们能够显示在胶原蛋白表达早期（E8.5-9.5），内源性基因先于转基因表达。但是，通过E11.5，总体模式将变得同步，只有少数例外。在成年组织中，内源性和转基因表达均被减弱，并且通过物理损伤或纤维原性细胞因子注射在各个器官中均被并行重新激活。这些发现表明，增强子对于I型胶原的激活至关重要，并且带有该增强子/报告子的小鼠提供了跟踪胶原基因转录活性和研究组织纤维化中细胞活性的有用模型。

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