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Notch信号通路能否成为肾脏疾病的一种潜在治疗选择?

Could Notch signaling pathway be a potential therapeutic option in renal diseases?

作者信息

Marquez-Exposito Laura, Cantero-Navarro Elena, Lavoz Carolina, Fierro-Fernández Marta, Poveda Jonay, Rayego-Mateos Sandra, Rodrigues-Diez Raúl R, Morgado-Pascual José Luis, Orejudo Macarena, Mezzano Sergio, Ruiz-Ortega Marta

机构信息

Laboratorio de Biología Celular en enfermedades renales, IIS-Fundación Jiménez Díaz-Universidad Autónoma de Madrid, Madrid, España.

División de Nefrología, Facultad de Medicina, Universidad Austral, Valdivia, Chile.

出版信息

Nefrologia (Engl Ed). 2018 Sep-Oct;38(5):466-475. doi: 10.1016/j.nefro.2017.11.027. Epub 2018 Feb 10.

Abstract

Notch pathway regulates key processes in the kidney, involved in embryonic development and tissue damage. In many human chronic renal diseases a local activation of Notch pathway has been described, suggesting that several components of Notch pathway could be considered as biomarkers of renal damage. Experimental studies by genetic modulation of Notch components or pharmacological approaches by γ-secretase inhibitors have demonstrated the role of this pathway in renal regeneration renal, podocyte apoptosis, proliferation and fibroblasts activation, and induction of epithelial to mesenchymal transition of tubular epithelial cells. Recent studies suggest an interaction between Notch and NF-κB pathway involved in the regulation of renal inflammatory process. On the other hand, there are some miRNAs that could regulate Notch components and down-stream responses. All these data suggest that Notch blockade could be a novel therapeutic option for renal diseases.

摘要

Notch信号通路调节肾脏中的关键过程,参与胚胎发育和组织损伤。在许多人类慢性肾脏疾病中,已经描述了Notch信号通路的局部激活,这表明Notch信号通路的几个成分可被视为肾脏损伤的生物标志物。通过对Notch成分进行基因调控或使用γ-分泌酶抑制剂进行药理学方法的实验研究已经证明了该信号通路在肾脏再生、足细胞凋亡、增殖和成纤维细胞激活以及诱导肾小管上皮细胞向间充质细胞转化中的作用。最近的研究表明,Notch信号通路与参与调节肾脏炎症过程的NF-κB信号通路之间存在相互作用。另一方面,有一些微小RNA可以调节Notch成分和下游反应。所有这些数据表明,Notch信号通路阻断可能是肾脏疾病的一种新的治疗选择。

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