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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Effects of PEP-1-FK506BP on cyst formation in polycystic kidney disease

  • Jo, Hyo Sang (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Eum, Won Sik (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Park, Eun Young (Department of Biological Science, Sookmyung Women's University) ;
  • Ko, Je Young (Department of Biological Science, Sookmyung Women's University) ;
  • Kim, Do Yeon (Department of Biological Science, Sookmyung Women's University) ;
  • Kim, Dae Won (Department of Biochemistry and Molecular Biology, Research Institute of Oral Sciences, College of Dentistry, Gangneung-Wonju National University) ;
  • Shin, Min Jea (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Son, Ora (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Cho, Su Bin (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Park, Jung Hwan (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Lee, Chi Hern (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Yeo, Eun Ji (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Yeo, Hyeon Ji (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Choi, Yeon Joo (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Youn, Jong Kyu (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Cho, Sung-Woo (Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine) ;
  • Park, Jinseu (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University) ;
  • Park, Jong Hoon (Department of Biological Science, Sookmyung Women's University) ;
  • Choi, Soo Young (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
  • Received : 2017.05.30
  • Accepted : 2017.07.20
  • Published : 2017.09.30
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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.

Keywords

References

  1. Wilson PD and Goilav B (2007) Cystic disease of the kidney. Annu Rev Patho 2, 341-368 https://doi.org/10.1146/annurev.pathol.2.010506.091850
  2. Pei Y and Watnick T (2010) Diagnosis and screening of autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis 17, 140-152 https://doi.org/10.1053/j.ackd.2009.12.001
  3. Harris PC and Torres VE (2009) Polycystic kidney disease. Annu Rev Med 60, 321-337 https://doi.org/10.1146/annurev.med.60.101707.125712
  4. Ye M, Grant M, Sharma M et al (1992) Cyst fluid from human autosomal dominant polycystic kidneys promotes cyst formation and expansion by renal epithelial cells in vitro. J Am Soc Nephrol 3, 984-994
  5. Yoder BK, Mulroy S, Eustace H, Boucher C and Sandford R (2006) Molecular pathogenesis of autosomal dominant polycystic kidney disease. Expert Rev Mol Med 8, 1-22
  6. Al-Bhalal L and Akhtar M (2008) Molecular basis of autosomal recessive polycystic kidney disease (ARPKD). Adv Anat Patho 15, 54-58 https://doi.org/10.1097/PAP.0b013e31815e5295
  7. Gardner KD Jr, Burnside JS, Elzinga LW and Locksley RM (1991) Cytokines in fluids from polycystic kidneys. Kidney Int 39, 718-724 https://doi.org/10.1038/ki.1991.87
  8. Park EY, Woo YM and Park JH (2011) Polycystic kidney disease and therapeutic approaches. BMB Rep 44, 359-368 https://doi.org/10.5483/BMBRep.2011.44.6.359
  9. Harada H, Furuya M, Ishikura H et al (2002) Expression of matrix metallo proteinase in the fluids of renal cystic lesions. J Urol 168, 19-22 https://doi.org/10.1016/S0022-5347(05)64822-7
  10. Liu B, Li C, Liu Z, Dai Z and Tao Y (2012) Increasing extracellular matrix collagen level and MMP activity induces cyst development in polycystic kidney disease. BMC Nephrol 13, 109 https://doi.org/10.1186/1471-2369-13-109
  11. Candiano G, Gusmano R, Altieri P et al (1992) Extracellular matrix formation by epithelial cells from human polycystic kidney cysts in culture. Virchows Arch B Cell Pathol Incl Mol Pathol 63, 1-9
  12. Lee EL, Song SA, Mun HW et al (2014) Blockage of interleukin-8 receptor signaling inhibits cyst development in vitro, via suppression of cell proliferation in autosomal polycystic kidney disease. Nephrol 19, 471-478 https://doi.org/10.1111/nep.12261
  13. Canaud G, Knebelmann B, Harris PC et al (2010) Therapeutic mTOR inhibition in autosomal dominant polycystic kidney disease: what is the appropriate serum level? Am J Transplant 10, 1701-1706 https://doi.org/10.1111/j.1600-6143.2010.03152.x
  14. Zafar I, Ravichandran K, Belibi FA, Doctor RB and Edelstein CL (2010) Sirolimus attenuates disease progression in an orthologous mouse model of human autosomal dominant polycystic kidney disease. Kidney Int 78, 754-761 https://doi.org/10.1038/ki.2010.250
  15. Wahl PR, Le Hir M, Vogetseder A et al (2007) Mitotic activation of Akt signalling pathway in Han:SPRD rats with polycystic kidney disease. Nephro 12, 357-363 https://doi.org/10.1111/j.1440-1797.2007.00811.x
  16. Ibraghimov-Beskrovnaya O and Natoli TA (2011) mTOR signaling in polycystic kidney disease. Trends Mol Med 17, 625-633 https://doi.org/10.1016/j.molmed.2011.06.003
  17. Fukuda R, Hirota K, Fan F et al (2002) Insulin-like growth factor 1 induces hypoxia-inducible factor 1-mediated vascular endothelial growth factor expression, which is dependent on MAP kinase and phosphatidylinositol 3-kinase signaling in colon cancer cells. J Biol Chem 277, 38205-38211 https://doi.org/10.1074/jbc.M203781200
  18. Zhong H, Chiles K, Feldser D et al (2000) Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res 60, 1541-1545
  19. Bae WY, Choi JS, Kim JE and Jeong JW (2015) Cinnamic aldehyde suppresses hypoxia-induced angiogenesis via inhibition of hypoxia-inducible factor-1alpha expression during tumor progression. Biochem Pharmacol 98, 41-50 https://doi.org/10.1016/j.bcp.2015.08.095
  20. Mi C, Ma J, Wang KS et al (2017) Imperatori suppresses proliferation and angiogenesis of human colon cancer cell by targeting HIF-$1{\alpha}$ via the mTOR/p70S6K/4E-BP1 and MAPK pathways. J Ethnopharmacol 203, 27-38 https://doi.org/10.1016/j.jep.2017.03.033
  21. Kang CB, Hong Y, Dhe-Paganon S and Yoon HS (2008) FKBP family proteins: immunophilins with versatile biological functions. Neurosignals 16, 318-325 https://doi.org/10.1159/000123041
  22. Harrar Y, Bellini C and Faure JD (2001) FKBPs: at the crossroads of folding and transduction. Trends Plant Sci 6, 426-431 https://doi.org/10.1016/S1360-1385(01)02044-1
  23. Pong K and Zaleska MM (2003) Therapeutic implications for immunophilin ligands in the treatment of neurodegenerative diseases. Curr Drug Targets CNS Neurol Disord 2, 349-356 https://doi.org/10.2174/1568007033482652
  24. Lopez-Ilasaca M, Schiene C, Kullertz G et al (1998) Effects of FK506-binding protein 12 and FK506 on autophosphorylation of epidermal growth factor receptor. J Biol Chem 273, 9430-9434 https://doi.org/10.1074/jbc.273.16.9430
  25. Costantini LC, Cole D, Chaturvedi P and Isacson O (2001) Immunophilin ligands can prevent progressive dopaminergic degeneration in animal models of Parkinson's disease. Eur J Neurosci 13, 1085-1092 https://doi.org/10.1046/j.0953-816x.2001.01473.x
  26. Guo X, Dawson VL and Dawson TM (2001) Neuroimmunophilin ligands exert neuroregeneration and neuroprotection in midbrain dopaminergic neurons. Eur J Neurosci 13, 1683-1693 https://doi.org/10.1046/j.0953-816x.2001.01542.x
  27. Ross DT, Guo H, Howorth P et al (2001) The small molecule FKBP ligand GPI 1046 induces partial striatal re-innervation after intranigral 6-hydroxydopamine lesion in rats. Neurosci Lett 297, 113-116 https://doi.org/10.1016/S0304-3940(00)01683-9
  28. Christner C, Herdegen T and Fischer G (2001) FKBP ligands as novel therapeutics for neurological disorders. Mini Rev Med Chem 1, 377-397 https://doi.org/10.2174/1389557013406675
  29. Avramut M and Achim CL (2002) Immunophilins and their ligands: Insights into survival and growth of human neurons. Physiol Behav 77, 463-468 https://doi.org/10.1016/S0031-9384(02)00934-4
  30. Dunlop EA and Tee AR (2009) Mammalian target of rapamycin complex 1: Signalling inputs, substrates and feedback mechanisms. Cell Signal 21, 827-835 https://doi.org/10.1016/j.cellsig.2009.01.012
  31. Garcia JA and Danielpour D (2008) Mammalian target of rapamycin inhibition as a therapeutic strategy in the management of urologic malignancies. Mol Cancer Ther 7, 1347-1354 https://doi.org/10.1158/1535-7163.MCT-07-2408
  32. Long C, Cook LG, Hamilton SL, Wu GY and Mitchell BM (2007) FK506 binding protein 12/12.6 depletion increases endothelial nitric oxide synthase threonine 495 phosphorylation and blood pressure. Hypertension 49, 569-576 https://doi.org/10.1161/01.HYP.0000257914.80918.72
  33. Raagel H, Saalik P and Pooga M (2010) Peptide-mediated protein delivery-which pathways are penetrable? Biochim Biophy Acta 1798, 2240-2248 https://doi.org/10.1016/j.bbamem.2010.02.013
  34. Liu Y, Wang S, Luo S et al (2016) Intravenous PEP-1-GDNF is protective after focal cerebral ischemia in rats. Neurosci Lett 617, 150-155 https://doi.org/10.1016/j.neulet.2016.02.017
  35. Kim SY, Sohn EJ, Kim DW et al (2011) Transduced PEP-1-K506BP ameliorates atopic dermatitis in NC/Nga mice. J Invest Dermatol 131, 1477-1485 https://doi.org/10.1038/jid.2011.49
  36. Kim DW, Lee SH, Shin MJ et al (2015) PEP-1-FK506BP inhibits alkali burn-induced corneal inflammation on the rat model of corneal alkali injury. BMB Rep 48, 618-623 https://doi.org/10.5483/BMBRep.2015.48.11.041
  37. Liu Y, Wang S, Luo S et al (2016) Intravenous PEP-1-GDNF is protective after focal cerebral ischemia in rats. Neurosci Lett 617, 150-155 https://doi.org/10.1016/j.neulet.2016.02.017
  38. Tan LG, Xiao JH, Yu DL et al (2015) PEP-1-SOD1 fusion proteins block cardiac myofibroblast activation and angiotensin II-induced collagen production. BMC Cardiovasc Disord 15, 116 https://doi.org/10.1186/s12872-015-0103-4
  39. Hwang HS, Park IY, Kim DW et al (2015) PEP-1-FK506BP12 inhibits matrix metalloproteinase expression in human articular chondrocytes and in a mouse carrageenan-induced arthritis model. BMB Rep 48, 407-412 https://doi.org/10.5483/BMBRep.2015.48.7.050
  40. Laplante M and Sabatini DM (2012) mTOR signaling in growth control and disease. Cell 149, 274-293 https://doi.org/10.1016/j.cell.2012.03.017
  41. Novalic Z, van der Wal AM, Leonhard WN et al (2012) Dose-dependent effects of sirolimus on mTOR signaling and polycystic kidney disease. J Am Soc Nephrol 23, 842-853 https://doi.org/10.1681/ASN.2011040340
  42. Serra AL, Poster D, Kistler AD et al (2010) Sirolimus and kidney growth in autosomal dominant polycystic kidney disease. N Engl J Med 363, 820-829 https://doi.org/10.1056/NEJMoa0907419
  43. Walz G, Budde K, Mannaa M et al (2010) Everolimus in patients with autosomal dominant polycystic kidney disease. N Engl J Med 363, 830-840 https://doi.org/10.1056/NEJMoa1003491
  44. Shillingford JM, Piontek KB, Germino GG and Weimbs T (2010) Rapamycin ameliorates PKD resulting from conditional inactivation of Pkd1. J Am Soc Nephrol 21, 489-497 https://doi.org/10.1681/ASN.2009040421
  45. Foster DA and Toschi A (2009) Targeting mTOR with rapamycin: one dose does not fit all. Cell Cycle 8, 1026-1029 https://doi.org/10.4161/cc.8.7.8044
  46. Chang ES, Park EY, Woo YM et al (2015) Restoring multidrug resistance-associated protein 3 attenuates cell proliferation in the polycystic kidney. Am J Physiol Renal Physiol 308, F1004-F1011 https://doi.org/10.1152/ajprenal.00159.2014
  47. Okada H, Ban S, Nagao S et al (2000) Progressive renal fibrosis in murine polycystic kidney disease: an immunohistochemical observation. Kidney Int 58, 587-597 https://doi.org/10.1046/j.1523-1755.2000.00205.x
  48. Ramasubbu K, Gretz N and Bachmann S (1998) Increased epithelial cell proliferation and abnormal extracellular matrix in rat polycystic kidney disease. J Am Soc Nephrol 9, 937-945
  49. Rankin CA, Itoh Y, Tian C et al (1999) Matrix metalloproteinase-2 in a murine model of infantile-type polycystic kidney disease. J Am Soc Nephrol 10, 210-217
  50. Watnick T and Germino GG (2010) mTOR inhibitor in polycystic kidney disease. N Egn J Med 363, 879-881 https://doi.org/10.1056/NEJMe1006925
  51. Bradford MA (1976) Rapid and sensitive method for the quantitation of microgram quantities utilizing the principle of protein-dye binding. Anal Biochem 72, 248-254 https://doi.org/10.1016/0003-2697(76)90527-3
  52. Jo HS, Yeo HJ, Cha HJ et al (2016) Transduced Tat-DJ-1 protein inhibits cytokines-induced pancreatic RINm5F cell death. BMB Rep 49, 297-302 https://doi.org/10.5483/BMBRep.2016.49.5.058
  53. Jo HS, Kim DS, Ahn EH et al (2016) Protective effects of Tat-NQO1 against oxidative stress-induced HT-22 cell damage, and ischemic injury in animals. BMB Rep 49, 617-622 https://doi.org/10.5483/BMBRep.2016.49.11.117

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