How is type I procoflagen synthesis regulated at the gene level during tissue fibrosis
How is type I procoflagen synthesis regulated at the gene level during tissue fibrosis
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DOI：
10.1002/jcb.10599
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发表时间：
2003-09-01
影响因子：
4
通讯作者：
Cutroneo, KR
中科院分区：
文献类型：
--
作者：
Cutroneo, KR
在对组织损伤的反应中，结缔组织的合成可以是正常的，也可以是异常的，这是由转化生长因子-β(TGF-β)和其他生长因子介导的。本文将主要关注损伤组织对转化生长因子-β在I型前胶原合成基因水平上的反应。这会导致临时修复，进而可能导致内陷、重塑、再生，并最终修复。或者，继续进行临时修复可能会导致纤维化并最终形成疤痕。肝脏和肺等内脏的疤痕会导致功能丧失，最终导致死亡。在皮肤结疤的情况下，这是一个美容问题，可以通过手术纠正。I型前胶原是由两个基因合成的，前α1(I型)和前α2(I型)胶原基因。本文将重点介绍这两个基因上调控特定基因转录的DNA结合部位。这篇文章还将定义前α1和前α2(I型)胶原基因启动的特定细胞信号通路。本文将解决几个问题。首先，在组织纤维化过程中，细胞外刺激前α1和前α2(I型)胶原基因转录的主要细胞因子是什么？其次，细胞外促纤维化细胞因子转化生长因子-β如何将信号从细胞膜传递到细胞核，以转录前α1(I型)和前α2(I型)胶原基因？第三，是什么信号通路与导致I型胶原基因表达的信号通路相互作用？第四，转化生长因子-β如何影响细胞外基质动态平衡？第五，与促进前α1(I型)和前α2(I型)胶原基因所需的DNA元件相对应的核因子是什么？最后，前α1(I型)和前α2(I型)胶原基因是如何协调调节的？还将提出减少纤维化的策略，纤维化是转化生长因子-β过度表达的结果。
In response to tissue injury connective tissue synthesis occurs either normally or abnormally, which is mediated by transforming growth factor-beta (TGF-beta) and other growth factors. This article will be primarily concerned with the response of injured tissues at the gene level of Type I procollagen synthesis in response to TGF-beta. This leads to provisional repair, which in turn may lead to involution, remodeling, regeneration, and ultimately repair. Alternately, continuation of provisional repair may lead to fibrosis and ultimately scarring. Scarring of internal organs such as the liver and the lung leads to loss of function and ultimately death. In the case of scarring of skin, this is a cosmetic problem and can be rectified by surgery. Type I procollagen is synthesized by two genes, proalpha1 (Type I) and proalpha2 (Type I) collagen genes. This article will focus on DNA binding sites on these two genes, which regulate the transcription of the specific gene. This article will also define specific cell signaling pathways for the turning on of the proalpha1 and proalpha2 (Type I) collagen genes. This article will address several questions. First, what is the major cytokine acting extracellularly which stimulates the transcription of the proalpha1 and proalpha2 (Type I) collagen genes during tissue fibrosis? Secondly, how are the signals transmitted by the extracellular profibrotic cytokine TGF-beta from the cellular membrane to the nucleus for transcription of the proalpha1 (Type I) and proalpha2 (Type I) collagen genes? Thirdly, what signaling pathways cross-talk with the signaling pathways resulting in the expression of the Type I collagen genes? Fourthly, how does TGF-beta affect extracellular matrix homeostasis? Fifthly, what are the nuclear factors corresponding to the DNA elements required for the promotion of the proalpha1 (Type I) and proalpha2 (Type I) collagen genes? Finally, how are the proalpha1 (Type I) and proalpha2 (Type I) collagen genes coordinately regulated? Strategies will also be presented for reducing fibrosis, which is the result of overexpression of TGF-beta.