본문 바로가기
KERD
논문KCI 등재

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

1

조회

0

다운로드

5

인용

0

참고문헌

키워드

주제분류화학

초록

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.

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.

참고문헌 (53)

  1. Wilson PD, "Cystic disease of the kidney", Annu Rev Patho, 2, pp.341~368 (2007)
  2. Pei Y, "Diagnosis and screening of autosomal dominant polycystic kidney disease", Adv Chronic Kidney Dis, 17, pp.140~152 (2010)
  3. Harris PC, "Polycystic kidney disease", Annu Rev Med, 60, pp.321~337 (2009)
  4. Ye M, "Cyst fluid from human autosomal dominant polycystic kidneys promotes cyst formation and expansion by renal epithelial cells in vitro", J Am Soc Nephrol, 3, pp.984~994 (1992)
  5. Yoder BK, "Molecular pathogenesis of autosomal dominant polycystic kidney disease", Expert Rev Mol Med, 8, pp.1~22 (2006)
  6. Al-Bhalal L, "Molecular basis of autosomal recessive polycystic kidney disease (ARPKD)", Adv Anat Patho, 15, pp.54~58 (2008)
  7. Gardner KD Jr, "Cytokines in fluids from polycystic kidneys", Kidney Int, 39, pp.718~724 (1991)
  8. 박은영, "Polycystic kidney disease and therapeutic approaches", BMB Reports, 44(6), pp.359~368 (2011), 생화학분자생물학회
  9. Harada H, "Expression of matrix metallo proteinase in the fluids of renal cystic lesions", J Urol, 168, pp.19~22 (2002)
  10. Liu B, "Increasing extracellular matrix collagen level and MMP activity induces cyst development in polycystic kidney disease", BMC Nephrol, 13, pp.109~ (2012)
  11. Candiano G, "Extracellular matrix formation by epithelial cells from human polycystic kidney cysts in culture", Virchows Arch B Cell Pathol Incl Mol Pathol, 63, pp.1~9 (1992)
  12. Lee EL, "Blockage of interleukin-8 receptor signaling inhibits cyst development in vitro, via suppression of cell proliferation in autosomal polycystic kidney disease", Nephrol, 19, pp.471~478 (2014)
  13. Canaud G, "Therapeutic mTOR inhibition in autosomal dominant polycystic kidney disease: what is the appropriate serum level?", Am J Transplant, 10, pp.1701~1706 (2010)
  14. Zafar I, "Sirolimus attenuates disease progression in an orthologous mouse model of human autosomal dominant polycystic kidney disease", Kidney Int, 78, pp.754~761 (2010)
  15. Wahl PR, "Mitotic activation of Akt signalling pathway in Han:SPRD rats with polycystic kidney disease", Nephro, 12, pp.357~363 (2007)
  16. Ibraghimov-Beskrovnaya O, "mTOR signaling in polycystic kidney disease", Trends Mol Med, 17, pp.625~633 (2011)
  17. Fukuda R, "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, pp.38205~38211 (2002)
  18. Zhong H, "Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor", phosphatidylinositol 3-kinase, AKT, pp.FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics, Cancer Res[DOI]
  19. Bae WY, "Cinnamic aldehyde suppresses hypoxia-induced angiogenesis via inhibition of hypoxia-inducible factor-1alpha expression during tumor progression", Biochem Pharmacol, 98, pp.41~50 (2015)
  20. Mi C, "Imperatori suppresses proliferation and angiogenesis of human colon cancer cell by targeting HIF-1 via the mTOR", p70S6K, J Ethnopharmacol, pp.2017, 203[DOI]
  21. Kang CB, "FKBP family proteins: immunophilins with versatile biological functions", Neurosignals, 16, pp.318~325 (2008)
  22. Harrar Y, "FKBPs: at the crossroads of folding and transduction", Trends Plant Sci, 6, pp.426~431 (2001)
  23. Pong K, "Therapeutic implications for immunophilin ligands in the treatment of neurodegenerative diseases", Curr Drug Targets CNS Neurol Disord, 2, pp.349~356 (2003)
  24. Lopez-Ilasaca M, "Effects of FK506-binding protein 12 and FK506 on autophosphorylation of epidermal growth factor receptor", J Biol Chem, 273, pp.9430~9434 (1998)
  25. Costantini LC, "Immunophilin ligands can prevent progressive dopaminergic degeneration in animal models of Parkinson’s disease", Eur J Neurosci, 13, pp.1085~1092 (2001)
  26. Guo X, "Neuroimmunophilin ligands exert neuroregeneration and neuroprotection in midbrain dopaminergic neurons", Eur J Neurosci, 13, pp.1683~1693 (2001)
  27. Ross DT, "The small molecule FKBP ligand GPI 1046 induces partial striatal re-innervation after intranigral 6-hydroxydopamine lesion in rats", Neurosci Lett, 297, pp.113~116 (2001)
  28. Christner C, "FKBP ligands as novel therapeutics for neurological disorders", Mini Rev Med Chem, 1, pp.377~397 (2001)
  29. Avramut M, "Immunophilins and their ligands: Insights into survival and growth of human neurons", Physiol Behav, 77, pp.463~468 (2002)
  30. Dunlop EA, "Mammalian target of rapamycin complex 1: Signalling inputs, substrates and feedback mechanisms", Cell Signal, 21, pp.827~835 (2009)
  31. Garcia JA, "Mammalian target of rapamycin inhibition as a therapeutic strategy in the management of urologic malignancies", Mol Cancer Ther, 7, pp.1347~1354 (2008)
  32. Long C, "FK506 binding protein 12", 12.6 depletion increases endothelial nitric oxide synthase threonine 495 phosphorylation and blood pressure, 2007, pp.49, 569~576
  33. Raagel H, "Peptide-mediated protein delivery-which pathways are penetrable?", Biochim Biophy Acta, 1798, pp.2240~2248 (2010)
  34. Liu Y, "Intravenous PEP-1- GDNF is protective after focal cerebral ischemia in rats", Neurosci Lett, 617, pp.150~155 (2016)
  35. Kim SY, "Transduced PEP-1-K506BP ameliorates atopic dermatitis in NC", Nga mice, 2011, pp.131, 1477~1485
  36. 김대원, "PEP-1-FK506BP inhibits alkali burn-induced corneal inflammation on the rat model of corneal alkali injury", BMB Reports, 48(11), pp.618~623 (2015), 생화학분자생물학회
  37. Liu Y, "Intravenous PEP-1- GDNF is protective after focal cerebral ischemia in rats", Neurosci Lett, 617, pp.150~155 (2016)
  38. Tan LG, "PEP-1-SOD1 fusion proteins block cardiac myofibroblast activation and angiotensin II-induced collagen production", BMC Cardiovasc Disord, 15, pp.116~ (2015)
  39. 황현숙, "PEP-1-FK506BP12 inhibits matrix metalloproteinase expression in human articular chondrocytes and in a mouse carrageenan-induced arthritis model", BMB Reports, 48(7), pp.407~412 (2015), 생화학분자생물학회
  40. Laplante M, "mTOR signaling in growth control and disease", Cell, 149, pp.274~293 (2012)
  41. Novalic Z, "Dose-dependent effects of sirolimus on mTOR signaling and polycystic kidney disease", J Am Soc Nephrol, 23, pp.842~853 (2012)
  42. Serra AL, "Sirolimus and kidney growth in autosomal dominant polycystic kidney disease", N Engl J Med, 363, pp.820~829 (2010)
  43. Walz G, "Everolimus in patients with autosomal dominant polycystic kidney disease", N Engl J Med, 363, pp.830~840 (2010)
  44. Shillingford JM, "Rapamycin ameliorates PKD resulting from conditional inactivation of Pkd1", J Am Soc Nephrol, 21, pp.489~497 (2010)
  45. Foster DA, "Targeting mTOR with rapamycin: one dose does not fit all", Cell Cycle, 8, pp.1026~1029 (2009)
  46. Chang ES, "Restoring multidrug resistance-associated protein 3 attenuates cell proliferation in the polycystic kidney", Am J Physiol Renal Physiol, 308, pp.F1004~F1011 (2015)
  47. Okada H, "Progressive renal fibrosis in murine polycystic kidney disease: an immunohistochemical observation", Kidney Int, 58, pp.587~597 (2000)
  48. Ramasubbu K, "Increased epithelial cell proliferation and abnormal extracellular matrix in rat polycystic kidney disease", J Am Soc Nephrol, 9, pp.937~945 (1998)
  49. Rankin CA, "Matrix metalloproteinase-2 in a murine model of infantile-type polycystic kidney disease", J Am Soc Nephrol, 10, pp.210~217 (1999)
  50. Watnick T, "mTOR inhibitor in polycystic kidney disease", N Egn J Med, 363, pp.879~881 (2010)
  51. Bradford MA, "Rapid and sensitive method for the quantitation of microgram quantities utilizing the principle of protein-dye binding", Anal Biochem, 72, pp.248~254 (1976)
  52. 조효상, "Transduced Tat-DJ-1 protein inhibits cytokines-induced pancreatic RINm5F cell death", BMB Reports, 49(5), pp.297~302 (2016), 생화학분자생물학회
  53. 조효상, "Protective effects of Tat-NQO1 against oxidative stress-induced HT-22 cell damage, and ischemic injury in animals", BMB Reports, 49(11), pp.617~622 (2016), 생화학분자생물학회

관련 논문AI추천

이 간행물의 다른 논문 (7건)