1. Effects of PEP-1-FK506BP on cyst formation in polycystic kidney disease.
- Author
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Jo HS, Eum WS, Park EY, Ko JY, Kim DY, Kim DW, Shin MJ, Son O, Cho SB, Park JH, Lee CH, Yeo EJ, Yeo HJ, Choi YJ, Youn JK, Cho SW, Park J, Park JH, and Choi SY
- Subjects
- Animals, Blotting, Western, Cell Proliferation genetics, Cell Proliferation physiology, Cysts genetics, Cysts metabolism, Disease Models, Animal, Humans, Microscopy, Confocal, Polycystic Kidney Diseases genetics, Signal Transduction genetics, Signal Transduction physiology, TOR Serine-Threonine Kinases genetics, Tacrolimus Binding Protein 1A genetics, Polycystic Kidney Diseases metabolism, TOR Serine-Threonine Kinases metabolism, Tacrolimus Binding Protein 1A metabolism
- 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].
- Published
- 2017
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