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PEP-1-FK506BP 对多囊肾病囊肿形成的影响。

Effects of PEP-1-FK506BP on cyst formation in polycystic kidney disease.

机构信息

Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 24252, Korea.

Department of Biological Science, Sookmyung Women's University, Seoul 04310, Korea.

出版信息

BMB Rep. 2017 Sep;50(9):460-465. doi: 10.5483/bmbrep.2017.50.9.090.

DOI:10.5483/bmbrep.2017.50.9.090

PMID:28760196

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5625693/

Abstract

Polycystic kidney disease (PKD) is one of the most common inherited disorders, involving progressive cyst formation in the kidney that leads to renal failure. FK506 binding protein 12 (FK506BP) is an immunophilin protein that performs multiple functions, including regulation of cell signaling pathways and survival. In this study, we determined the roles of PEP-1-FK506BP on cell proliferation and cyst formation in PKD cells. Purified PEP-1-FK506BP transduced into PKD cells markedly inhibited cell proliferation. Also, PEP-1-FK506BP drastically inhibited the expression levels of p-Akt, p-p70S6K, p-mTOR, and p-ERK in PKD cells. In a 3D-culture system, PEP-1-FK506BP significantly reduced cyst formation. Furthermore, the combined effects of rapamycin and PEP-1-FK506BP on cyst formation were markedly higher than the effects of individual treatments. These results suggest that PEP-1-FK506BP delayed cyst formation and could be a new therapeutic strategy for renal cyst formation in PKD. [BMB Reports 2017; 50(9): 460-465].

摘要

多囊肾病（PKD）是最常见的遗传疾病之一，涉及肾脏中进行性囊肿形成，导致肾衰竭。FK506 结合蛋白 12（FK506BP）是一种免疫亲和素蛋白，具有多种功能，包括调节细胞信号通路和存活。在本研究中，我们确定了 PEP-1-FK506BP 在 PKD 细胞中的细胞增殖和囊肿形成中的作用。纯化的 PEP-1-FK506BP 转导到 PKD 细胞中可显著抑制细胞增殖。此外，PEP-1-FK506BP 还显著抑制 PKD 细胞中 p-Akt、p-p70S6K、p-mTOR 和 p-ERK 的表达水平。在 3D 培养系统中，PEP-1-FK506BP 可显著减少囊肿形成。此外，雷帕霉素和 PEP-1-FK506BP 的联合作用对囊肿形成的影响明显高于单独治疗的影响。这些结果表明，PEP-1-FK506BP 可延迟囊肿形成，可能成为 PKD 中肾脏囊肿形成的新治疗策略。[BMB 报告 2017；50（9）：460-465]。