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Twist:腹膜间皮细胞上皮-间充质转化中的新角色。

Twist: a new player in the epithelial-mesenchymal transition of the peritoneal mesothelial cells.

出版信息

Nephrol Dial Transplant. 2012 Nov;27(11):3978-81. doi: 10.1093/ndt/gfs172. Epub 2012 Jul 13.

Abstract

BACKGROUND

The peritoneal membrane is a vital structure for peritoneal dialysis (PD) patients. It has been increasingly recognized that the transition of the peritoneal lining mesothelial cells into a more fibroblastic phenotype is a key step in peritoneal membrane injury.

METHODS

Relevant literature was reviewed and summarized.

RESULTS

Epithelial-to-mesenchymal transition (EMT) is a basic cellular process that occurs in a variety of physiologic and pathologic processes. The hallmark of this process is a loss of epithelial markers, and E-cadherin is a prototypical epithelial transmembrane protein. E-cadherin expression is suppressed at many levels and the gene is regulated by a family of transcription factors. Twist is one of the lesser studied E-cadherin regulatory factors, which belongs to a larger family of basic helix-loop-helix DNA-binding proteins. In this issue of Nephrology Dialysis Transplantation, Cuixiang Li reports on in vitro experiments where the expression of Twist led to a decreased expression of E-cadherin and the evidence of EMT. In an in vivo model of dialysate exposure, Li demonstrates that Twist expression is increased in the injured peritoneal tissues.

CONCLUSIONS

These important observations are the first to link Twist to mesothelial cell EMT and peritoneal membrane injury. Like most novel observations, this paper leaves many questions unanswered. Twist is only one of several transcription factors involved in EMT and how these factors interact will require further investigations. Furthermore, the question of whether Twist interacts at multiple levels in the EMT process, or simply gives an initial push to the process, is left unanswered. Finally, to bring these early significant findings to the bedside as potential therapies for PD patients will require further innovation.

摘要

背景

腹膜是腹膜透析(PD)患者的重要结构。人们越来越认识到,腹膜衬里间皮细胞向更成纤维细胞表型的转变是腹膜损伤的关键步骤。

方法

综述相关文献。

结果

上皮间质转化(EMT)是一种发生在多种生理和病理过程中的基本细胞过程。这一过程的标志是上皮标志物的丧失,E-钙黏蛋白是典型的上皮跨膜蛋白。E-钙黏蛋白的表达在多个水平受到抑制,基因受转录因子家族的调控。Twist 是研究较少的 E-钙黏蛋白调节因子之一,属于更大的碱性螺旋-环-螺旋 DNA 结合蛋白家族。在本期《肾脏病与透析移植杂志》上,李秀春报告了体外实验,其中 Twist 的表达导致 E-钙黏蛋白表达减少和 EMT 的证据。在透析液暴露的体内模型中,李证明 Twist 表达在受损的腹膜组织中增加。

结论

这些重要的观察结果首次将 Twist 与间皮细胞 EMT 和腹膜膜损伤联系起来。像大多数新的观察结果一样,本文留下了许多未回答的问题。Twist 只是参与 EMT 的几个转录因子之一,这些因子如何相互作用将需要进一步的研究。此外,Twist 是否在 EMT 过程的多个水平上相互作用,或者只是对该过程起到初始推动作用,这一问题尚未得到解答。最后,要将这些早期的重要发现转化为 PD 患者的潜在治疗方法,还需要进一步的创新。

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