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Effects of PEP-1-FK506BP on cyst formation in polycystic kidney disease
Soo Young Choi1,*, Hyo Sang Jo1,#, Won Sik Eum1,#, Eun Young Park2,#, Je Young Ko2, Do Yeon Kim2, Dae Won Kim3, Min Jea Shin1, Su Bin Cho1, Jung Hwan Park1, Chi Hern Lee1, Eun Ji Yeo1, Hyeon Ji Yeo1, Yeon Joo Choi1, Sung-Woo Cho4
1Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University,
2Biological Science, Sookmyung Women’s University,
3Biochemistry and Molecular Biology, Research Institute of Oral Sciences, Gangneung-Wonju National University,
4Biochemistry and Molecular Biology, University of Ulsan College of Medicine
Abstract
Polycystic kidney disease (PKD) is one of the most common inherited disorders, whereby progressive cyst formation in the kidney leads to renal failure. FK506 binding protein 12 (FK506BP) is an immunophilin protein which performs multiple functions including regulation of cell signaling 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 and 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 those of individual treatments. These results suggest that the PEP-1-FK506BP delays cyst formation and could be a new therapeutic strategy for renal cyst formation in PKD.
Abstract, Accepted Manuscript(in press) [Submitted on May 30, 2017, Accepted on July 20, 2017]
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