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Том 10 №2 2008 год - Нефрология и диализ

Аутосомно-доминантная поликистозная болезнь почек: новые патогенетические и терапевтические аспекты

Ермоленко В.М. Батэрдэнэ С.

Аннотация: Еще Гиппократу были известны 4 болезни почек, две из которых с современных позиций классифицируются как мочекаменная и связанная с уретеральной обструкцией, третью не удается идентифицировать, а четвертая, представляет, по-видимому, описание поликистозной болезни почек и рекомендации по ее лечению, включая хирургическое (вскрытие абсцессов], хотя исходы хирургических вмешательств в то время в большинстве случаев были неутешительными. Даже Galen, врачевавший раны у гладиаторов и обладавший определенными хирургическими приемами, в своих трактатах не упоминал о хирургическом лечении болезней почек. Не исключают, что живший в VI веке Aetius, описавший макрогематурию при поднятии тяжести, падении с высоты и т. д., имел в виду больных с кистозным заболеванием почек.

Для цитирования: Ермоленко В.М., Батэрдэнэ С. Аутосомно-доминантная поликистозная болезнь почек: новые патогенетические и терапевтические аспекты. Нефрология и диализ. 2008. 10(2):111-122. doi:

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Ключевые слова: аутосомно-доминантная поликистозная болезнь почек: новые патогенетические и терапевтические аспекты, первичная цилия, механизмы цистогенезиса

Список литературы:

1. Кутырина И.М. Поликистоз почек. “Нефрология” Руководство для врачей. Ред. И. Е. Тареева. М.: Медицина 2000: 437-444.
2. Кутырина И. М. Кистозные болезни почек. “Нефрология”. Учебное пособие для послевузовского образования, Издат. группа “ГЭОТАР-Медиа” М.: 2007: 459-469.
3. Ausley S., Badano J., Blacque O. et al. Basal body dysfunction is a likely cause of pleiotropic Bardet-Biedl syndrome. Nature 2003; 425: 628-633.
4. Bach S., Knockaert M., Reinhart J. et al. Roscovitine targets, protein kinases and pyridoxal kinase. J Biol Chem 2005; 280: 31208-31219.
5. Badano J., Mistuma N., Beales P., Katsanis N. The ciliopathies: an emerging class of human genetic disorders. Annu Rev Genomics Hum Genet 2006; 7: 125-148.
6. Beligi F., Reif G., Wallace D. et al. Cyclic AMP promotes growth and secretion in human polycystic kidney epithelial cells. Kidney int 2004; 66: 964-971.
7. Bello-Reuss E., Holubec K., Rajaraman S. Angiogenesis in autosomal dominant polycystic kidney disease. Kidney int 2001; 60: 37-45.
8. Benson C., White J., De Bono. et al. A phase I trial of the selective oral cyclin-dependent kinase inhibitor seliciclib (CYC 201; R-Roscovitine), administered twice daily for 7 days every 21 days. Br J Cancer 2007; 96: 29-37.
9. Bhatt A., Kaverina I., Otey C., Huttenlocher A. Regulation of focal complex composition and disassembly by the calcium-dependent protease calpain. J Cell Sci 2002; 115 (Pt 17): 3415-3425.
10. Bhunia A., Piontek K., Boletta A. et al. PKD1 induced p21 (waf 1) and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2. Cell 2002; 109: 157-168.
11. Blacque O., Reardon M., McCarty J. et al. Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport. Genes Dev 2004; 18: 1630-1642.
12. Blaneo G. NaK-ATPase subunit heterogeneity as a mechanism for tissue-specific ion regulation. Semin Nephrol 2005; 25: 292-303.
13. Boca M., Distefano Q., Qian F. et al. Polycystin-1 induces resistance to apoptosis through the phosphatidylinositol 3-kinase/Akt signaling pathway. J Am Soc Nephrol 2006; 17: 637-647.
14. Boletta A., Qian F., Onuchic L. et al. Polycystin-1, the gene product of PKD1, induces resistance to apoptosis and spontaneous tubulogenesis in MDCK cells. Mol Cell 2000; 6: 1267-1273.
15. Bonetus T. Sepulchretum sive anatomica practica ex cadaveribus morbo denatis. Cramer and Perachon, Leiden 1700.
16. Bottinger E., Bitzer M. TGF-b signaling in renal disease. J Am Soc Nephrol 2002; 13: 2600-2610.
17. Boutler C., Mulroy S., Well S. et al. Cardiovascular skeletal and renal defects in mice with targeted disruption of the Pkd1 gene. Proc Natl Acad Sci USA 2001; 98: 12174-12179.
18. Brasier J., Henske E. Loss of the polycystic kidney disease (PKD1) region on chromosome 16p13 in renal cyst cells supports a loss of function model for cyst pathogenesis. J Clin Investig 1997; 99: 194-199.
19. Bristowe F. Cystic disease of the liver, associated with similar disease of the kidneys. Transaction of the Pathological Society of London 1856; 7: 229-234.
20. Brown N., Murcia N. Delayed cystogenesis and increased ciliogenesis associated with re-expression of polaris in Tg 737 mutant mice. Kidney int 2003; 63: 1220-1229.
21. Bukanov N., Smith L., Klinger K. et al. Long-lasting arrest of murine polycystic kidney disease with CDK inhibitor roscovitine. Nature 2006; 444: 949-952.
22. Bunting C. Congenital cystic kidney and liver with familial tendency. J Exp Med 1925; 18: 359-370.
23. Burrow C., Devuyst O., Li X. et al. Expression of the b2-subunit and apical localization of NaK-ATPase in metanephric kidney. Am J Physiol 1999; 277: F391-F403.
24. Cairns H. Heredity in polycystic disease of the kidneys. Quart J Med 1925; 18: 359-370.
25. Cano D., Murcia N., Pazour G., Hearok M. Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organization. Development 2004; 131: 3457-3467.
26. Chapman A. Autosomal dominant polycystic kidney disease: time for a change? J. Am Soc Nephrol 2007; 18: 1399-1407.
27. Chapman A., Guuy-Woodford L., Grantham J. et al. The Consortium for radiological imaging studies (CRIS) of polycystic kidney disease cohort: renal structure in early autosomal dominant polycystic kidney disease (ADPKD). Kidney int 2003; 64: 2214-2221.
28. Chapman A., Torres V., Grantham J. et al. A phase II B pilot study of the safety and efficacy of Tolvaptan, a vasopressin V2 receptor antagonist (V2RA), in patients with ADPKD. J Am Soc Nephrol 2006; 16: 68A.
29. Chatterjee S., Shi W., Wilson P., Mazumdar A. Role of lactosylceramide and MAP kinase in proliferation of proximal tubular cells in human polycystic kidney disease. J Lipid Res 1996; 37: 1334-1344.
30. Cordit K., Acanstad P., Singla V. et al. Vertebrate smoothened functions at the primary cilium. Nature 2005; 437: 1018-1021.
31. Couvelaire A. Sur degenerescence kystique congenitale des organes glandularies et en particulier des reins et du foie. Annales de gynecologie et obstetriques 1899; 52: 453.
32. Cowley B., Rupp J. Abnormal expression of epidermal growth factor and sulfated glycoprotein SGP-2 messenger RNA in a rat model of autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1995; 6: 1679-1681.
33. Cruveilhier J. Anatomie pathologique du corps humain. Paris: 1852; 1: 1829-1835.
34. Dalgaard O. Bilateral polycystic disease of the kidneys: a follow-up study of 284 patients and their families. Acta Med Scand 1957; 158; S328: 1-255.
35. Davenport J., Yoder B. An incredible decade for the primary cilium: a look at once-forgotten organelle. Am J Physiol 2005; 289: F1159-F1169.
36. Davidow C., Maser R., Rome L. et al. The cystic fibrosis transmembrane conductance regulator mediates transepithelial fluid secretion by human autosomal dominant polycystic disease epithelium in vivo. Kidney int 1996; 50: 208-218.
37. Devuyst O., Burron C., Schweibert E. et al. Developmental regulation CFTR expression during human nephrogenesis. Am J Physiol 1996; 271: F723-F735.
38. Devuyst O., Burron C., Suith B. et al. Expression of aquaporins-1 and -2 during nephrogenesis and in autosomal dominant polycystic kidney disease. Am J Physiol 1996; 271: F169-F183.
39. Du J., Wilson P. Abnormal polarization of EGF receptors and autocrine stimulation of cyst epithelial growth in human ADPKD. Am J Physiol 1995; 269: C487-C495.
40. Ecder T., Edelstein C., Fick-Brosnahan G. et al. Diuretics versus angiotensin-converting enzyme inhibitors in autosomal dominant polycystic kidney disease. Am J Nephrol 2001; 21: 98-103.
41. Feraille E., Doucet A. Sodium-potassium-adenosintriphosphatase-dependent sodium transport in the kidney: Hormonal control. Physiol Rev 2001; 81: 345-418.
42. Fisher E., Legue E., Doyen A. et al. Defective planar cell polarity in polycystic kidney disease. Nat Genet 2006; 38: 21-23.
43. Fogazzi G. The description of polycystic kidney by Domenico Gusmano Galeazzi. NDT 1998; 13: 1039-1040.
44. Gattone V. Emerging therapies for polycystic kidney disease. Curr Opinion Pharm 2005; 5: 535-542.
45. Gattone V., Andrews G., Nin F. et al. Defective epidermal growth factor gene expression in mice with polycystic kidney disease. Develop Biol 1990; 138: 225-230.
46. Gattone V., Ricker J., Trambaugh C. et al. Multiorgan mRNA misexpression in murine autosomal recessive polycystic kidney disease. Kidney int 2002; 62: 1590-1599.
47. Gattone V., Wang X., Harris P., Torres V. Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist. Nature Med 2003; 9: 1323-1326.
48. Geug L., Burrow C., Li H., Wilson P. Modification of the composition of polycystin-1 multiprotein complex by calcium and tyrosine phosphorylation. Biochem Biophys Acta 2000; 1535: 21-35.
49. Gile R., Cowley B., Cattone V. et al. Effect of lovastatin on the development of polycystic kidney disease in the Han:SPRD rat. Am J Kidney Dis 1995; 26: 501-507.
50. Grantham J. Renal cell proliferation and the two face of cyclic adenosine monophosphate. J Lab Clin Med 1997; 130: 459-460.
51. Grantham J., Chapman A., Torres V. Volume progression in autosomal dominant polycystic kidney disease: the major factor determining clinical outcomes. Clin J Am Soc Nephrol 2006; 1: 148-157.
52. Grantham J., Torres V., Chapman A. et al. Volume progression in polycystic kidney disease. N Engl J Med 2006; 354: 2122-2130.
53. Grantham J., Ye M., Davidow C. et al. Evidence for potent lipid secretogogue in the cyst fluid of patient with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 1995; 6: 1242-1249.
54. Grimm D., Cai Y., Chanvet V. et al. Polycystin-1 distribution is modulated by polycystin-2 expression in mammalion cells. J Biol Chem 2003; 278: 36786-36793.
55. Handel M., Sehulz S., Stanarius M. et al. Selective targeting of somatostatin reseptor 3 to neuronal cilia. Neuroscience 1999; 89: 909-926.
56. Harris P., Bae K., Rossetti S. et al. Cyst number but not the rate of cystic growth is associated with the mutated gene in autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2006; 17: 3013-3019.
57. Haycraft C., Banizs B., Aydin-Son Y. et al. Gli 2 и Gli 3 localize to cilia and require the intraflagellar transport proteins polaris for processing and function. Plos Genet 2005; 1: e53.
58. Hou X., Mrug M., Yoder B. et al. Cystin, a novel cilia-associated protein, is disrupted in the cpk mouse model of polycystic kidney disease. J Clin Investig 2002; 109: 533-540.
59. Husson H., Manavalan P., Akmaev V. et al. New insights into ADPKD molecular pathways using combination of SAGE and microarray technologies. Genomics 2004; 84: 497-510.
60. Ibraghimov-Beskrovnaya O. Targeting dysregulated cell cycle and apoptosis for polycystic kidney disease therapy. Cell Cycle 2007; 6: 776-779.
61. Igarashi P., Somlo S. Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol 2002; 13: 2384-2398.
62. Inoki K., Corradetti M., Guan K. Dysregulation of the TSC-mTOR pathway in human disease. Nat Genet 2005; 37: 19-24.
63. Jafar T., Stark P., Schmidt C. et al. The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease. Kidney int 2005; 67: 265-271.
64. Johnson K., Rosenbaum J. Polariry of flagellar assembly in Chlamydomonas J Cell Biol 1992; 119: 1605-1611.
65. Kim E., Arnould T., Sellin L. et al. The polycystic kidney disease 1 gene product modulates Wnt signaling. J Biol Chem 1999; 274: 4947-4953.
66. Klahr S., Breyer J., Beck G. et al. Dietary protein restriction blood pressure control and the progression of polycystic kidney disease. Modification of Diet in Renal Disease Study Group. J. Am. Soc. Nephrol 1995; 5: 2037-2047.
67. Kocaman O., Oflaz H., Yekeber E. et al. Endothelial dysfunction and increased carotid intima-media thikness in patients with autosomal dominant polycystic kidney disease. Am J Kidney Dis 2004; 43: 854-860.
68. Koulen P., Cai Y., Geug L. et al. Polycystin-2 is an intracellular calcium release channel. Nat Cell Biol 2002; 4: 191-197.
69. Kozminski K., Johnson K., Forscher P., Rosenbaum J.A. Motility in the eukaryotic flagellum unrelated to flagellar beating. Proc Natl Acad Sci US 1993; 90: 5519-5523.
70. Kramer-Zucker A., Olale F., Haycraft C. et al. Cilia driven fluid flow in the zebrafish pronephrons, brain and kupffer vesicle is required for normal organogenesis. Development 2005; 132: 1907-1921.
71. Kuo N., Norman J., Wilson P. Acidic FGF regulation of hyperproliferation of fibroblast in human autosomal dominant polycystic kidney disease. Biochem Mol Med 1997; 61: 178-191.
72. Lebeau C., Hanaoka K., Moore-Hoon M. et al. Basolateral chloride transporters in autosomal dominant polycystic kidney disease. Eur J Physiol 2002; 444: 722-731.
73. Lejars F. Du gros rein polykystique de adulte. Paris: Steinhei 1888.
74. Li H., Amsler K., Hyink D. et al. PRKX, a phylogenetically and functionally distinct cAMP-dependent protein kinase, activates renal epithelial cell migration and morphogenesis. Proc Natl Acad Sci USA 2002; 99: 9260-9265.
75. Li H., Geng L., Burow., Wilson P. Identification of phosphorylation sites in the PKD-1 encoded protein C-terminal domain. Biochem Biophys Res Commun 1999; 259: 356-363.
76. Li X., Hyink P., Polgar K. et al. Protein kinase x activities ureteric bud branching morphogenesis in developing mouse metanephric kidney. J Am Soc Nephrol 2005; 16: 3543-3522.
77. Li X., Luo Y., Starremans P. et al. Polycystin 1 and polycystin 2 regulate the cell cycle through the helix-loop-helix inhibitor Id2. Nat Cell Biol 2005; 7: 1202-1212.
78. Lin F., Hiesberger T., Cordes K. et al. Kidney specific inactivation of the KIF3A subunit of kinesin-II inhibits renal ciliogenesis and produces polycystic kidney disease. Proc Natl Acad Sci USA 2003; 100: 5286-5291.
79. Low S., Vasanth S., Larson C. et al. Polycystin-1, STAT6 and P100 function in a pathway that transduces ciliary mechanosensation and is activated in polycystic kidney disease. Dev Cell 2006; 10: 57-69.
80. Lowden D., Lindemann G., Merlino G. et al. Renal cysts in transgenic mice, expressing transforming growth factor-alpha. J Lab Clin Med 1994; 124: 386-394.
81. MacRae D., Nemo K., Sweeney W., Avner E. EGF-regulated growth factors in the pathogenesis of murine ARPKD. Kidney int 2004; 65: 2018-2029.
82. Marquardt W. Cystenniere, Cystenleber and Cystenpankreas. Tübingen 1934.
83. Masyuk A., Masyuk T., Splinter P. et al. Cholangiocyte cilia defect changes in luminal fluid flow and transmit them into intracellular Ca2+ and cAMP signaling. Gastroenterology 2006; 131: 911-920.
84. Mobasheri A., Avila J., Cozar-Castellano I. et al. Na+K+-ATPase isoenzime diversity; comparative biochemistry and physiological implications of novel functional interactions. Biosci Rep 2000; 20: 51-91.
85. Mochizuki T., Wu G., Hayashi T. et al. PKD2, a gene for polycystic kidney disease, that encodes integral membrane protein. Science 1996; 272: 1339-1342.
86. Morgagni J. The Seats and Causes of Diseases Investigated by Anatomy. translated by B. Alexcander et al. London: 1769; 1-3.
87. Mostov K. mTOR is out of control in polycystic kidney disease. Proc Natl Acad Sci USA 2006; 103: 5247-5248.
88. Motte S. de la, Gianella-Boradori A. Pharmacokinetic model of R-roscovitine and its metabolite in healthy male subjects. Int J Clin Pharmacol Ther 2004; 42: 232-239.
89. Nagano J., Kitamura K., Hujer K. et al. Fybrocystin interacts with CAML, a protein, involved in calcium signaling. Biochem Biophys Res Commun 2005; 338: 880-889.
90. Nagao S., Nishii K., Katsuyama M. et al. Increased water intake decreases progression of polycystic kidney disease in the PCK rat. J Am Soc Nephrol 2006; 17: 2220-2277.
91. Nakamura T., Ebihara I., Fukui M. et al. Increased endothelin and endothelin receptor mRNA expression in polycystic kidney disease of cpk mice. J Am Soc Nephrol 1993; 4, 1064-1072.
92. Nakanishi K., Sweeney W., Avner E. Segment-specific c-ErbB2 expression in human autosomal recessive polycystic kidney disease. J Am Soc Nephrol 2001; 12: 379-384.
93. Nauli S., Aleughat F., Luo Y. et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of the kidney cells. Nat Genet 2003; 33: 129-137.
94. Nauli S., Rossetti S., Kolb R. et al. Loss of polycystin-1 in human cyst-lining epithelia leads to ciliary dysfunction. J Am Soc Nephrol 2006; 17: 1015-1025.
95. Nauta J., Sweeney W., Rutledge J. et al. Biliary epithelial cells from mice with congenital polycystic kidney disease are hyperresponsive to epidermal growth factor. Pediatr Res 1995; 37: 755-763.
96. Nishio S., Hatano M., Nagata M. et al. Pkd1 regulates immortalized proliferation of renal tubular epithelial cells through p53 induction and JNK activation. J Clin Investig 2005; 115: 910-918.
97. Norman J., Wilson P. Extracellular matrix metabolism in human autosomal dominant polycystic kidney disease. Contrib Nephrol 1996; 118: 126-134.
98. Orellana S., Sweeney W., Neff C. et al. Epidermal growth factor expression is abnormal in murine polycystic kidney. Kidney int 1995; 47: 490-499.
99. Park T., Gray R., Sato A. et al. Subcellular localization and signaling properties of Dishevelled in developing vertebrate embryos. Curr Biol 2005; 15: 1039-1044.
100. Pazour G., Dickert B., Vucica Y. et al. Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene Tg 737, are required for assembly of cilia and flagella. J Cell Biol 2000; 151: 709-718.
101. Pazour G., Agustin J., Follit J. et al. Polycystin-2 localizes to kidney cilia and the ciliary level is elevated in orpk mice with polycystic kidney disease. Curr Biol 2002; 12: R378-R380.
102. Peral B., Ong A., San Millan J. et al. A stable nonsense mutation associated with a case of infantible onset polycystic kidney disease (PKD1). Hum Mol Gen 1996; 5: 539-542.
103. Perautoni A. Renal development. Perspectives of Wnt-dependent process. Semin Cell Dev Biol 2003; 14: 201-208.
104. Persu A., Stoenouin M., Messiaen T. et al. Modifier effect of eNOS in autosomal dominant polycystic kidney disease. Hum Mol Genet 2002; 11: 229-241.
105. Polgar K., Burrow C., Hyink D. et al. Disruption of polycystin-1 function interferes with branching morphogenesis of the ureteric bud in developing mouse kidney. Dev Biol 2005; 286: 16-30.
106. Praetorius H., Spring K. Bending the MDCK cell primary cilium increases intracellular calcium. J Membr Biol 2001; 184: 71-79.
107. Praetorius H., Spring K. Removal of the MDCK cell primary cilium abolishes flow sensing. J Membr Biol 2003; 191: 69-76.
108. Qian F., Watnick T., Onuchic L., Germino G. The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type 1. Cell 1996; 87: 979-987.
109. Qian Q., Hunter L., Li M. et al. PKD2 haploinsufficiency alters intracellular calcium regulation in vascular smooth muscle cell. Hum Mol Genet 2003; 12: 1875-1880.
110. Qin N., Burnette D., Bae Y. et al. Intraflagellar transport is required for the vectorial movement of TRPV channels in the ciliary membrane. Curr Biol 2005; 15: 1695-1699.
111. Quarmly L., Parker J. Cilia and the cell cycle? J Cell Biol 2005; 169: 707-710.
112. Rayer P. Atlas in traite des maladies des reins. Paris: 1841.
113. Remuzzi G., Bertani T. Mechanism of disease. Pathophysiology of progressive nephropathies. N Engl J Med 1998; 339: 1448-1456.
114. Ricker J., Gattone V., Calvet J. et al. Development of autosomal recessive polycystic kidney disease in BALB/c-cpk/cpk mice. J Am Soc Nephrol 2000; 11: 1837-1847.
115. Ricker J., Mata J., Iversen P., Cattone V. C-myc antisense oligonucleotide treatment ameliorates murine ARPKD. Kidney int 2002; 61 (Suppl. 1): 125-131.
116. Rohatsi R., Greenberg A., Burron C. et al. Na transport in autosomal recessive polycystic kidney disease (ARPKD) cyst lining epithelial cells. J Am Soc Nephrol 2003; 14: 827-836.
117. Roitback T., Surviladze Z., Tikkanen R., Wandinger-Ness A. A polycystin multiprotein complex constitutes a cholesterol-containing signaling microdomain in human kidney epithelia. Biochem J 2005; 392 (Pt 1): 29-38.
118. Roitbak T., Ward C., Harris P. A polycystin 1 multiprotein complex is disrupted in polycystic kidney disease cells. Mol Biol Cell 2004; 15: 1134-1146.
119. Ruggenenti P., Remuzzi A., Ondei P. et al. Safety and efficacy of long-acting somatostatin treatment in autosomal dominant polycystic kidney disease. Kidney int 2005; 68: 206-216.
120. Saadi-Kheddouci S., Berrebi D., Romagunbo B. et al. Early development of polycystic kidney disease in transgenic mice expressing an activated mutant of the beta-catenin gene. Oncogene 2001; 20: 5972-5981.
121. Scholey J. Intraflagellar transport. Annu Rev Cell Dev Biol 2003; 19: 423-443.
122. Schrier R., McFann K., Johnson A. et al. Cardiac and renal effects of standart versus rigorous blood pressure control in autosomal dominant polycystic kidney disease: results of a seven-year prospective randomized study. J Am Soc Nephrol 2002; 13: 1733-1739.
123. Schwiebert E., Wallace D., Braunstein G. et al. Autocrine extracellular purinergic signaling in epithelial cells derived from polycystic kidney. Am J Physiol 2002; 282: F763-F775.
124. Shillingford J., Murcia N., Larson C. et al. The mTOR pathway is regulated by polycystin-1 and its inhibition reverses cystogenesis in polycystic kidney disease. Proc Nat Acad Sci USA 2006; 103: 5466-5471.
125. Simons M., Glay J., Ganner A. et al. Inversin, the gene product, mutated in nephrophthisis type II, function as molecular switch between Wnt signaling pathways. Nat Genet 2005; 37: 537-543.
126. Siugla V., Reiter J. The primary cilium as the cells antenna: signaling at a sensory organelle. Science 2006; 313: 629-633.
127. Smith L., Husson H. et al. Development of polycystic kidney disease in juvenile cystic kidney mice: insights into pathogenesis, ciliary abnormalities and common features with human disease. J Am Soc Nephrol 2006; 17: 2821-2831.
128. Steiner P. Ueber grosscystische Degeneration der Nieren und der Leber. Deutsche med. Wocheschr. 1899; 25: 677-678.
129. Stoetzel C., Muller J., Laurier V. et al. Identification of novel BBS gene (BBS12) highlights the mayor role of vertebrate-specific branch of chaperonin-related proteins in Bardet-Biedl syndrome. Am J Hum Genet 2007; 80: 1-11.
130. Sweadner K., Rael E. The FXYD gene family of small ion transport regulators or channels: cDNA sequence, protein signature sequence and expression. Genomics 2000; 68: 41-56.
131. Sweeney W., Awner E. Functional activity of epidermal growth factor receptors in autosomal recessive polycystic kidney disease. Am J Physiol 1998; 275: F387-F394.
132. Sweeney W., Chen Y., Nakanishi K. et al. Treatment of polycystic kidney disease with a novel tyrosine kinase inhibitor. Kidney int 2000; 57: 33-40.
133. Tao Y., Kim J., Fanbel S. et al. Caspase inhibition reduces tubular apoptosis and proliferation and slows disease progression in polycystic kidney disease. Proc Natl Acad Sci USA 2005; 102: 6954-6959.
134. Tao Y., Kim J., Schrier R. et al. Rapamycin markedly slows disease progression in rat model of polycystic kidney disease. J Am Soc Nephrol 2005; 16: 46-51.
135. Taulman P., Haycraft C., Balkovetz D. et al. Polaris, a protein inviolved in left-right axis pattering, localizes to basal bodies and cilia. Mol Biol Cell 2001; 12: 589-599.
136. Teilmann S., Byscov A., Pedersen P. et al. Localization of transient receptor potential ion channels in primary and motile cilia of the female murine reproductive organs. Mol Reprod Dev 2005; 71: 444-452.
137. Torres V. Cyclic AMP, at the hub of the cystic cycle. Kidney int 2004; 66: 1283-1285.
138. Torres V., Sweeney W., Wang X. et al. EGF receptor tyrosine kinase inhibition attenuates the development of PKD in Han:SPRD rats. Kidney int 2003; 64: 1573-1579.
139. Torres V., Sweeney W., Wang X. et al. EGF receptor tyrosine kinase inhibition in not effective in PCK rats. Kidney int 2004; 66: 1766-1773.
140. Torres V., Wang X., Qain Q. et al. Effective treatment of orthologous model of autosomal dominant of polycystic kidney disease. Nature Med 2004; 10: 363-364.
141. Trudel M., Chretien M., D'Agati V. Disappearance of polycystic kidney disease in revertant c-myc transgenic mice. Mamm Genome 1994; 5: 149-152.
142. Trudel M., D'Agati V., Constantini F. C-myc as an inducer of polycystic disease in transgenic mice. Kidney int 1991; 39: 665-671.
143. Tsiokas L., Arnould T., Zhu C. et al. Specific association of the gene product of PKD2 with TRPC1 channel. Proc Natl Acad Sci USA 1999; 96: 3934-3939.
144. Van Dijk M., Kamper A., van Veen S. et al. Effect of simvastatin on renal function in autosomal dominant polycystic kidney disease. NDT 2001; 16: 2152-2157.
145. Wahl P., Serra A., Le Hiz M. et al. Inhibition mTOR with sirolimus slows disease progression in Han:SPKD rats. NDT 2006; 21: 598-604.
146. Wallingford J., Habas R. The developmental biology of cell polarity. Development 2005; 132: 4421-4436.
147. Walz G. Therapeutic approaches in autosomal dominant polycystic kidney disease (ADPKD): is there light at the end of the tunnel? NDT 2006; 21: 1752-1757.
148. Wang Q., Pan J., Suell W. Intraflagellar transport particles participate directly in cilium-generated signaling in Chlamydomonas. Cell 2006; 125: 549-562.
149. Wang X., Gattone V., Harris P., Torres V. Effectiveness of vasopressin V2 receptor antagonists OPC-31260 and OPC-41061 on polycystic kidney disease development in the PCK rat. J Am Soc Nephrol 2005; 16: 846-851.
150. Weinstein T., Hwang D., Lev-Ran A. et al. Excretion of epidermal growth factor in human adult polycystic kidney disease. Isr J Med Sci 1997; 33: 641-642.
151. Wildman S., Hooker K., Turner C. et al. The isolated polycystin-1 cytoplasmic COOH terminus prolongs ATP-stimulated Cl¯conductance through increased Ca2+ entry. J Am Physiol 2003; 285: F1168-F1178.
152. Wilks S. Cystic disease of the liver and kidney. Transaction of the Pathological Society of London 1856; 7: 235-237.
153. Wilson P. Epithelial cell polarity and disease. Am J Physiol 1997; 272: F4343-F442.
154. Wilson P. Pathogenesis of polycystic kidney disease: altered cellular function. In: Polycystic kidney disease. ed. M. Watson, V. Torres. Oxford Univ Press 1996: 125-163.
155. Wilson P. Polycystic kidney disease. New Engl J Med 2004; 350: 151-164.
156. Wilson P., Devuyst O., Li X. et al. Apical plasma membrane mispolarization of NaK-ATPase in polycystic kidney disease epithelia is associated with aberrant expression of the b2 isoform. Am J Pathol 2000; 156: 253-268.
157. Wilson P., Du J., Norman J. Autocrine, endocrine and paracrine regulation of growth abnormalities in autosomal dominant polycystic kidney disease Eur J Cell Biol 1993; 61: 131-138.
158. Wilson P., Geug I., Li X., Burrow C. The PKD-1 gene product “polycystin-1” in tyrosine phosphorylated protein that colocalizes with a2 b1-integrin in focal clusters in adherent renal epithelia. Lab Investig 1999; 79: 1311-1323.
159. Wilson P., Hovater J., Casey C. et al. ATP release mechanisms in primary cultures of epithelia derived from the cysts of polycystic kidneys. J Am Soc Nephrol 1999; 10: 218-229.
160. Wilson S., Amsler K., Hyink D. et al. Inhibition of Her-2 (new/ErbB2) restores normal function and structure to polycystic kidney disease (PKD) epithelia. Biochem Biohys Acta 2006; 1762: 647-655.
161. Woo D. Apoptosis and loss of renal tissue in polycystic kidney disease. N Engl J Med 1995; 333: 18-25.
162. Wullschleger S., Loewith R., Hall M. TOR signaling in growth and metabolism. Cell 2006; 124: 471-484.
163. Yamaguchi T., Delling J., Ramaswamy N. et al. Cyclic AMP stimulates the in vitro proliferation of renal cyst epithelial cell by activating the extracellular signal regulated kinase pathway. Kidney int 2000; 57: 1460-1471.
164. Yamaguchi T., Hempson S., Reif G. et al. Calcium restores a normal proliferation phenotype in human polycystic kidney disease epithelial cells. Am J Soc Nephrol 2006; 17: 178-187.
165. Yamaguchi T., Nagao S., Wallace D. et al. Cyclic AMP activated B-Raf and ERK in cyst epithelial cells from autosomal dominant polycystic kidneys. Kidney int 2003; 63: 1983-1994.
166. Yamamura Y., Nakamura S., Itoh S. et al. OPC-41061, a highly potent human vasopressin V2-receptor antagonist: pharmacological profile and aquaretic effect by single and multiple oral dosing in rats. J Pharmacol Exp Ther 1998; 287: 860-867.
167. Yoder B., Hou X., Guay-Woodford L. The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris and cystin are co-localited in renal cilia J Am Soc Nephrol 2002; 13: 2508-2516.
168. Yoder B., Richards W., Sweeney W. et al. Insertional mutagenesis and molecular analysis of a new gene associated with polycystic kidney disease. Proc Assoc Am Physicians 1995; 107: 314-323.
169. Yoder B., Tousson A., Millican L. et al. Polaris, a protein disrupted in orpk mutant mice, is required for assembly of renal cilium. Am J Physiol 2002; 282: F541-F552.
170. Zatti A., Chavet V., Rajendran V. et al. The C-terminal tail of the polycystin-1 protein interacts with the NaK-ATPase a-subunit. Mol Biol Cell 2005; 16: 5087-5093.
171. Zeier M., Fehrenlack P., Geberth S. et al. Renal histology and polycystic kidney disease with incipient and advanced renal failure. Kidney int 1992; 42: 1259-1265.
172. Zeisberg M., Strutz F., Muller G. Renal fibrose: an update. Curr Opin Nephrol Hypertens 2001; 10: 315-320.
173. Zhang Q., Davenport R., Croyle M. et al. Disruption of IFT results in both exocrine and endocrine abnormalities in the pancreas of Tg737 (orpk) mutant mice. Lab. Investig 2005; 85: 45-64.
174. Zimmerman K. Contributing to the knowledge of glands and epithelium. Arch Mikr Eutwicklungsmech 1898; 52: 552-706.