Kidney: Polycystic kidney disease

Wiley Interdisciplinary Reviews: Developmental Biology

Volumn 3, Issue 6, 2014, Pages 465-487

  Paul, Binu M ^a   Vanden Heuvel, Gregory B ^b,c  

^a MAYO CLINIC   (United States)

^b WESTERN MICHIGAN UNIVERSITY HOMER STRYKER MD SCHOOL OF MEDICINE   (United States)

^c WHEATON COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA TOXIN; BETA CATENIN; CYCLIC AMP; CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE INHIBITOR 1A; GLYCOGEN SYNTHASE KINASE 3BETA; GUANINE NUCLEOTIDE BINDING PROTEIN; LIPOXYGENASE; MONOCYTE CHEMOTACTIC PROTEIN 1; PHOSPHOLIPASE C; POLYCYSTIN; POLYCYSTIN 1; POLYCYSTIN 2; TOLL LIKE RECEPTOR 4; TRANSCRIPTION FACTOR AP 1; WNT PROTEIN;

AUTOSOMAL DOMINANT DISORDER; AUTOSOMAL RECESSIVE DISORDER; BARDET BIEDL SYNDROME; CELL DIFFERENTIATION; CELL POLARITY; CELL PROLIFERATION; DEVELOPMENTAL DISORDER; DYSOSTOSIS; END STAGE RENAL DISEASE; EXTRACELLULAR MATRIX; FETUS DEVELOPMENT; GENE EXPRESSION; GENE MUTATION; GERMLINE MUTATION; GROWTH REGULATION; HUMAN; IMAGING SYSTEM; INNATE IMMUNITY; KIDNEY CYST; KIDNEY DEVELOPMENT; KIDNEY FAILURE; KIDNEY HYPERTROPHY; KIDNEY POLYCYSTIC DISEASE; KIDNEY TRANSPLANTATION; MODIFIER GENE; NEPHRONOPHTHISIS; NONHUMAN; NUCLEOLAR LOCALIZATION SIGNAL; PRIORITY JOURNAL; REVIEW; SECRETION (PROCESS); SOMATIC MUTATION; WNT SIGNALING PATHWAY; ANIMAL; BIOLOGICAL MODEL; EMBRYOLOGY; GENE EXPRESSION REGULATION; GENETICS; KIDNEY; MECHANOTRANSDUCTION; PATHOLOGY;

ANIMALS; GENE EXPRESSION REGULATION, DEVELOPMENTAL; HUMANS; KIDNEY; MECHANOTRANSDUCTION, CELLULAR; MODELS, BIOLOGICAL; POLYCYSTIC KIDNEY DISEASES; WNT SIGNALING PATHWAY;

EID: 84911469453     PISSN: 17597684     EISSN: 17597692     Source Type: Journal    
DOI: 10.1002/wdev.152     Document Type: Review

References (155)

1. Grantham JJ. Polycystic kidney disease: huge kidneys, huge problems, huge progress. Trans Am Clin Climatol Assoc 1997, 108:165-170 discussion 70-2.
2. Igarashi P, Somlo S. Genetics and pathogenesis of polycystic kidney disease. J Am Soc Nephrol 2002, 13:2384-2398.
3. Harris PC, Torres VE. Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease. J Clin Invest 2014, 124:2315-2324.
4. Gallagher AR, Germino GG, Somlo S. Molecular advances in autosomal dominant polycystic kidney disease. Adv Chronic Kidney Dis 2010, 17:118-130.
5. Hou X, Mrug M, Yoder BK, Lefkowitz EJ, Kremmidiotis G, D'Eustachio P, Beier DR, Guay-Woodford LM. Cystin, a novel cilia-associated protein, is disrupted in the cpk mouse model of polycystic kidney disease. J Clin Invest 2002, 109:533-540.
6. Ekser B, Rigotti P. Images in clinical medicine. Autosomal dominant polycystic kidney disease. N Engl J Med 2010, 363:71.
7. Grantham JJ. Polycystic kidney disease: a predominance of giant nephrons. Am J Physiol 1983, 244:F3-F10.
8. Brown JA. Images in clinical medicine. End-stage autosomal dominant polycystic kidney disease. N Engl J Med 2002, 347:1504.
9. Woo D. Apoptosis and loss of renal tissue in polycystic kidney diseases. N Engl J Med 1995, 333:18-25.
10. Guay-Woodford LM, Desmond RA. Autosomal recessive polycystic kidney disease: the clinical experience in North America. Pediatrics 2003, 111:1072-1080.
11. Parfrey PS. Autosomal-recessive polycystic kidney disease. Kidney Int 2005, 67:1638-1648.
12. Guay-Woodford LM. Renal cystic diseases: diverse phenotypes converge on the cilium/centrosome complex. Pediatr Nephrol 2006, 21:1369-1376.
13. Ibraghimov-Beskrovnaya O, Bukanov N. Polycystic kidney diseases: from molecular discoveries to targeted therapeutic strategies. Cell Mol Life Sci 2008, 65:605-619.
14. Gabow PA. Autosomal dominant polycystic kidney disease. N Engl J Med 1993, 329:332-342.
15. Reed BY, McFann K, Bekheirnia MR, Nobakhthaghighi N, Masoumi A, Johnson AM, Shamshirsaz AA, Kelleher CL, Schrier RW. Variation in age at ESRD in autosomal dominant polycystic kidney disease. Am J Kidney Dis 2008, 51:173-183.
16. Shamshirsaz AA, Reza Bekheirnia M, Kamgar M, Johnson AM, McFann K, Cadnapaphornchai M, Nobakhthaghighi N, Schrier RW. Autosomal-dominant polycystic kidney disease in infancy and childhood: progression and outcome. Kidney Int 2005, 68:2218-2224.
17. Yoder BK, Hou X, Guay-Woodford LM. The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. J Am Soc Nephrol 2002, 13:2508-2516.
18. Hughes J, Ward CJ, Peral B, Aspinwall R, Clark K, San Millán JL, Gamble V, Harris PC. The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains. Nat Genet 1995, 10:151-160.
19. Martinez JR, Grantham JJ. Polycystic kidney disease: etiology, pathogenesis, and treatment. Dis Mon 1995, 41:693-765.
20. Gabow PA, Johnson AM, Kaehny WD, Kimberling WJ, Lezotte DC, Duley IT, Jones RH. Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. Kidney Int 1992, 41:1311-1319.
21. Torres VE, Harris PC. Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int 2009, 76:149-168.
22. Steinman TI. Polycystic kidney disease: a new perspective from the beginning. Kidney Int 2005, 68:2398-2399.
23. Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet 2007, 369:1287-1301.
24. Ong AC, Harris PC. Molecular pathogenesis of ADPKD: the polycystin complex gets complex. Kidney Int 2005, 67:1234-1247.
25. Paul BM, Consugar MB, Ryan Lee M, Sundsbak JL, Heyer CM, Rossetti S, Kubly VJ, Hopp K, Torres VE, Coto E, et al. Evidence of a third ADPKD locus is not supported by re-analysis of designated PKD3 families. Kidney Int 2014, 85:383-392.
26. Grantham JJ, Cook LT, Wetzel LH, Cadnapaphornchai MA, Bae KT. Evidence of extraordinary growth in the progressive enlargement of renal cysts. Clin J Am Soc Nephrol 2010, 5:889-896.
27. Shokeir MH. Expression of "adult" polycystic renal disease in the fetus and newborn. Clin Genet 1978, 14:61-72.
28. Bae K, Park B, Sun H, Wang J, Tao C, Chapman AB, Torres VE, Grantham JJ, Mrug M, Bennett WM, et al. Segmentation of individual renal cysts from MR images in patients with autosomal dominant polycystic kidney disease. Clin J Am Soc Nephrol 2013, 8:1089-1097.
29. Saxen L. Oraganogenesis of the Kidney. Cambridge, UK: Cambridge University Press; 1987.
30. Bouchard M. Transcriptional control of kidney development. Differentiation 2004, 72:295-306.
31. Lipschutz JH. Molecular development of the kidney: a review of the results of gene disruption studies. Am J Kidney Dis 1998, 31:383-397.
32. Schedl A, Hastie ND. Cross-talk in kidney development. Curr Opin Genet Dev 2000, 10:543-549.
33. Dressler GR. The cellular basis of kidney development. Annu Rev Cell Dev Biol 2006, 22:509-529.
34. Dressler GR. Advances in early kidney specification, development and patterning. Development 2009, 136:3863-3874.
35. Lechner MS, Dressler GR. The molecular basis of embryonic kidney development. Mech Dev 1997, 62:105-120.
36. Potter SS, Brunskill EW, Patterson LT. Defining the genetic blueprint of kidney development. Pediatr Nephrol 2011, 26:1469-1478.
37. Bernhardt WM, Schmitt R, Rosenberger C, Münchenhagen PM, Gröne HJ, Frei U, Warnecke C, Bachmann S, Wiesener MS, Willam C, et al. Expression of hypoxia-inducible transcription factors in developing human and rat kidneys. Kidney Int 2006, 69:114-122.
38. Costantini F, Kopan R. Patterning a complex organ: branching morphogenesis and nephron segmentation in kidney development. Dev Cell 2010, 18:698-712.
39. Brophy PD, Ostrom L, Lang KM, Dressler GR. Regulation of ureteric bud outgrowth by Pax2-dependent activation of the glial derived neurotrophic factor gene. Development 2001, 128:4747-4756.
40. Grieshammer U, Ma L, Plump AS, Wang F, Tessier-Lavigne M, Martin GR. SLIT2-mediated ROBO2 signaling restricts kidney induction to a single site. Dev Cell 2004, 6:709-717.
41. Kume T, Deng K, Hogan BL. Murine forkhead/winged helix genes Foxc1 (Mf1) and Foxc2 (Mfh1) are required for the early organogenesis of the kidney and urinary tract. Development 2000, 127:1387-1395.
42. Basson MA, Akbulut S, Watson-Johnson J, Simon R, Carroll TJ, Shakya R, Gross I, Martin GR, Lufkin T, McMahon AP, et al. Sprouty1 is a critical regulator of GDNF/RET-mediated kidney induction. Dev Cell 2005, 8:229-239.
43. Basson MA, Watson-Johnson J, Shakya R, Akbulut S, Hyink D, Costantini FD, Wilson PD, Mason IJ, Licht JD. Branching morphogenesis of the ureteric epithelium during kidney development is coordinated by the opposing functions of GDNF and Sprouty1. Dev Biol 2006, 299:466-477.
44. Michos O, Gonçalves A, Lopez-Rios J, Tiecke E, Naillat F, Beier K, Galli A, Vainio S, Zeller R. Reduction of BMP4 activity by gremlin 1 enables ureteric bud outgrowth and GDNF/WNT11 feedback signalling during kidney branching morphogenesis. Development 2007, 134:2397-2405.
45. Kreidberg JA, Sariola H, Loring JM, Maeda M, Pelletier J, Housman D, Jaenisch R. WT-1 is required for early kidney development. Cell 1993, 74:679-691.
46. Wellik DM, Hawkes PJ, Capecchi MR. Hox11 paralogous genes are essential for metanephric kidney induction. Genes Dev 2002, 16:1423-1432.
47. Gong KQ, Yallowitz AR, Sun H, Dressler GR, Wellik DM. A Hox-Eya-Pax complex regulates early kidney developmental gene expression. Mol Cell Biol 2007, 27:7661-7668.
48. O'Brien LL, McMahon AP. Progenitor programming in mammalian nephrogenesis. Nephrology (Carlton) 2013, 18:177-179.
49. Patel SR, Dressler GR. The genetics and epigenetics of kidney development. Semin Nephrol 2013, 33:314-326.
50. Parnell SC, Magenheimer BS, Maser RL, Zien CA, Frischauf AM, Calvet JP. Polycystin-1 activation of c-Jun N-terminal kinase and AP-1 is mediated by heterotrimeric G proteins. J Biol Chem 2002, 277:19566-19572.
51. Moy GW, Mendoza LM, Schulz JR, Swanson WJ, Glabe CG, Vacquier VD. The sea urchin sperm receptor for egg jelly is a modular protein with extensive homology to the human polycystic kidney disease protein, PKD1. J Cell Biol 1996, 133:809-817.
52. Ward CJ, Turley H, Ong AC, Comley M, Biddolph S, Chetty R, Ratcliffe PJ, Gattner K, Harris PC. Polycystin, the polycystic kidney disease 1 protein, is expressed by epithelial cells in fetal, adult, and polycystic kidney. Proc Natl Acad Sci USA 1996, 93:1524-1528.
53. Bateman A, Sandford R. The PLAT domain: a new piece in the PKD1 puzzle. Curr Biol 1999, 9:R588-R590.
54. Chauvet V, Qian F, Boute N, Cai Y, Phakdeekitacharoen B, Onuchic LF, Attié-Bitach T, Guicharnaud L, Devuyst O, Germino GG, et al. Expression of PKD1 and PKD2 transcripts and proteins in human embryo and during normal kidney development. Am J Pathol 2002, 160:973-983.
55. Chapin HC, Caplan MJ. The cell biology of polycystic kidney disease. J Cell Biol 2010, 191:701-710.
56. Chauvet V, Tian X, Husson H, Grimm DH, Wang T, Hiesberger T, Igarashi P, Bennett AM, Ibraghimov-Beskrovnaya O, Somlo S, et al. Mechanical stimuli induce cleavage and nuclear translocation of the polycystin-1 C terminus. J Clin Invest 2004, 114:1433-1443.
57. Zhou J. Polycystins and primary cilia: primers for cell cycle progression. Annu Rev Physiol 2009, 71:83-113.
58. Knepper MA, Pisitkun T. Exosomes in urine: who would have thought...? Kidney Int 2007, 72:1043-1045.
59. Hogan MC, Manganelli L, Woollard JR, Masyuk AI, Masyuk TV, Tammachote R, Huang BQ, Leontovich AA, Beito TG, Madden BJ, et al. Characterization of PKD protein-positive exosome-like vesicles. J Am Soc Nephrol 2009, 20:278-288.
60. Semmo M, Köttgen M, Hofherr A. The TRPP subfamily and polycystin-1 proteins. Handb Exp Pharmacol 2014, 222:675-711.
61. Ong AC, Ward CJ, Butler RJ, Biddolph S, Bowker C, Torra R, Pei Y, Harris PC. Coordinate expression of the autosomal dominant polycystic kidney disease proteins, polycystin-2 and polycystin-1, in normal and cystic tissue. Am J Pathol 1999, 154:1721-1729.
62. Geng L, Segal Y, Pavlova A, Barros EJ, Löhning C, Lu W, Nigam SK, Frischauf AM, Reeders ST, Zhou J. Distribution and developmentally regulated expression of murine polycystin. Am J Physiol 1997, 272:F451-F459.
63. Markowitz GS, Cai Y, Li L, Wu G, Ward LC, Somlo S, D'Agati VD. Polycystin-2 expression is developmentally regulated. Am J Physiol 1999, 277:F17-F25.
64. Qian F, Watnick TJ, Onuchic LF, Germino GG. The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. Cell 1996, 87:979-987.
65. Pei Y. A "two-hit" model of cystogenesis in autosomal dominant polycystic kidney disease? Trends Mol Med 2001, 7:151-156.
66. Harris PC. What is the role of somatic mutation in autosomal dominant polycystic kidney disease? J Am Soc Nephrol 2010, 21:1073-1076.
67. Lu W, Peissel B, Babakhanlou H, Pavlova A, Geng L, Fan X, et al. Perinatal lethality with kidney and pancreas defects in mice with a targetted Pkd1 mutation. Nat Genet 1997, 17:179-181.
68. Wu G, D'Agati V, Cai Y, Markowitz G, Park JH, Reynolds DM, et al. Somatic inactivation of Pkd2 results in polycystic kidney disease. Cell 1998, 93:177-188.
69. Pritchard L, Sloane-Stanley JA, Sharpe JA, Aspinwall R, Lu W, Buckle V, et al. A human PKD1 transgene generates functional polycystin-1 in mice and is associated with a cystic phenotype. Hum Mol Genet 2000, 9:2617-2627.
70. Thivierge C, Kurbegovic A, Couillard M, Guillaume R, Cote O, Trudel M. Overexpression of PKD1 causes polycystic kidney disease. Mol Cell Biol 2006, 26:1538-1548.
71. Lantinga-van Leeuwen IS, Dauwerse JG, Baelde HJ, Leonhard WN, van de Wal A, Ward CJ, Verbeek S, Deruiter MC, Breuning MH, de Heer E. Lowering of Pkd1 expression is sufficient to cause polycystic kidney disease. Hum Mol Genet 2004, 13:3069-3077.
72. Rossetti S, Kubly VJ, Consugar MB, Hopp K, Roy S, Horsley SW, Chauveau D, Rees L, Barratt TM, van't Hoff WG, et al. Incompletely penetrant PKD1 alleles suggest a role for gene dosage in cyst initiation in polycystic kidney disease. Kidney Int 2009, 75:848-855.
73. Vujic M, Heyer CM, Ars E, Hopp K, Markoff A, Orndal C, Rudenhed B, Nasr SH, Torres VE, Torra R, et al. Incompletely penetrant PKD1 alleles mimic the renal manifestations of ARPKD. J Am Soc Nephrol 2010, 21:1097-1102.
74. Hopp K, Ward CJ, Hommerding CJ, Nasr SH, Tuan HF, Gainullin VG, Rossetti S, Torres VE, Harris PC. Functional polycystin-1 dosage governs autosomal dominant polycystic kidney disease severity. J Clin Invest 2012, 122:4257-4273.
75. Piontek K, Menezes LF, Garcia-Gonzalez MA, Huso DL, Germino GG. A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1. Nat Med 2007, 13:1490-1495.
76. Lantinga-van Leeuwen IS, Leonhard WN, van der Wal A, Breuning MH, de Heer E, Peters DJ. Kidney-specific inactivation of the Pkd1 gene induces rapid cyst formation in developing kidneys and a slow onset of disease in adult mice. Hum Mol Genet 2007, 16:3188-3196.
77. Takakura A, Contrino L, Beck AW, Zhou J. Pkd1 inactivation induced in adulthood produces focal cystic disease. J Am Soc Nephrol 2008, 19:2351-2363.
78. Takakura A, Contrino L, Zhou X, Bonventre JV, Sun Y, Humphreys BD, Zhou J. Renal injury is a third hit promoting rapid development of adult polycystic kidney disease. Hum Mol Genet 2009, 18:2523-2531.
79. Bell PD, Fitzgibbon W, Sas K, Stenbit AE, Amria M, Houston A, Reichert R, Gilley S, Siegal GP, Bissler J, et al. Loss of primary cilia upregulates renal hypertrophic signaling and promotes cystogenesis. J Am Soc Nephrol 2011, 22:839-848.
80. Weimbs T. Third-hit signaling in renal cyst formation. J Am Soc Nephrol 2011, 22:793-795.
81. Weimbs T. Polycystic kidney disease and renal injury repair: common pathways, fluid flow, and the function of polycystin-1. Am J Physiol Renal Physiol 2007, 293:F1423-F1432.
82. Patel V, Li L, Cobo-Stark P, Shao X, Somlo S, Lin F, Igarashi P. Acute kidney injury and aberrant planar cell polarity induce cyst formation in mice lacking renal cilia. Hum Mol Genet 2008, 17:1578-1590.
83. Sharma N, Malarkey EB, Berbari NF, O'Connor AK, Vanden Heuvel GB, Mrug M, Yoder BK. Proximal tubule proliferation is insufficient to induce rapid cyst formation after cilia disruption. J Am Soc Nephrol 2013, 24:456-464.
84. Berbari NF, O'Connor AK, Haycraft CJ, Yoder BK. The primary cilium as a complex signaling center. Curr Biol 2009, 19:R526-R535.
85. Hildebrandt F, Benzing T, Katsanis N. Ciliopathies. N Engl J Med 2011, 364:1533-1543.
86. Hildebrandt F, Otto E. Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease? Nat Rev Genet 2005, 6:928-940.
87. Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet 2003, 33:129-137.
88. Yamaguchi T, Hempson SJ, Reif GA, Hedge AM, Wallace DP. Calcium restores a normal proliferation phenotype in human polycystic kidney disease epithelial cells. J Am Soc Nephrol 2006, 17:178-187.
89. Arnould T, Kim E, Tsiokas L, Jochimsen F, Grüning W, Chang JD, Walz G. The polycystic kidney disease 1 gene product mediates protein kinase C alpha-dependent and c-Jun N-terminal kinase-dependent activation of the transcription factor AP-1. J Biol Chem 1998, 273:6013-6018.
90. Le NH, van der Wal A, van der Bent P, Lantinga-van Leeuwen IS, Breuning MH, van Dam H, de Heer E, Peters DJ. Increased activity of activator protein-1 transcription factor components ATF2, c-Jun, and c-Fos in human and mouse autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2005, 16:2724-2731.
91. Puri S, Magenheimer BS, Maser RL, Ryan EM, Zien CA, Walker DD, Wallace DP, Hempson SJ, Calvet JP. Polycystin-1 activates the calcineurin/NFAT (nuclear factor of activated T-cells) signaling pathway. J Biol Chem 2004, 279:55455-55464.
92. Lanoix J, D'Agati V, Szabolcs M, Trudel M. Dysregulation of cellular proliferation and apoptosis mediates human autosomal dominant polycystic kidney disease (ADPKD). Oncogene 1996, 13:1153-1160.
93. Weimbs T, Olsan EE, Talbot JJ. Regulation of STATs by polycystin-1 and their role in polycystic kidney disease. JAK-STAT 2013, 2:e23650-1-e23650-9.
94. Bhunia AK, Piontek K, Boletta A, Liu L, Qian F, Xu PN, Germino FJ, Germino GG. PKD1 induces p21(waf1) 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.
95. Felekkis KN, Koupepidou P, Kastanos E, Witzgall R, Bai CX, Li L, Tsiokas L, Gretz N, Deltas C. Mutant polycystin-2 induces proliferation in primary rat tubular epithelial cells in a STAT-1/p21-independent fashion accompanied instead by alterations in expression of p57KIP2 and Cdk2. BMC Nephrol 2008, 9:10. doi: 10.1186/1471-2369-9-10.
96. Li X, Luo Y, Starremans PG, McNamara CA, Pei Y, Zhou J. Polycystin-1 and polycystin-2 regulate the cell cycle through the helix-loop-helix inhibitor Id2. Nat Cell Biol 2005, 7:1202-1212.
97. Low SH, Vasanth S, Larson CH, Mukherjee S, Sharma N, Kinter MT, Kane ME, Obara T, Weimbs T. 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.
98. Olsan EE, Mukherjee S, Wulkersdorfer B, Shillingford JM, Giovannone AJ, Todorov G, Song X, Pei Y, Weimbs T. Signal transducer and activator of transcription-6 (STAT6) inhibition suppresses renal cyst growth in polycystic kidney disease. Proc Natl Acad Sci USA 2011, 108:18067-18072.
99. Talbot JJ, Shillingford JM, Vasanth S, Doerr N, Mukherjee S, Kinter MT, Watnick T, Weimbs T. Polycystin-1 regulates STAT activity by a dual mechanism. Proc Natl Acad Sci USA 2011, 108:7985-7990.
100. Shillingford JM, Murcia NS, Larson CH, Low SH, Hedgepeth R, Brown N, Flask CA, Novick AC, Goldfarb DA, Kramer-Zucker A, et al. The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease. Proc Natl Acad Sci USA 2006, 103:5466-5471.
101. Dere R, Wilson PD, Sandford RN, Walker CL. Carboxy terminal tail of polycystin-1 regulates localization of TSC2 to repress mTOR. PLoS One 2010, 5:e9239.
102. Huber TB, Walz G, Kuehn EW. mTOR and rapamycin in the kidney: signaling and therapeutic implications beyond immunosuppression. Kidney Int 2011, 79:502-511.
103. Watnick T, Germino GG. mTOR inhibitors in polycystic kidney disease. N Engl J Med 2010, 363:879-881.
104. Kim E, Arnould T, Sellin LK, Benzing T, Fan MJ, Grüning W, Sokol SY, Drummond I, Walz G. The polycystic kidney disease 1 gene product modulates Wnt signaling. J Biol Chem 1999, 274:4947-4953.
105. Lal M, Song X, Pluznick JL, Di Giovanni V, Merrick DM, Rosenblum ND, Chauvet V, Gottardi CJ, Pei Y, Caplan MJ. Polycystin-1 C-terminal tail associates with beta-catenin and inhibits canonical Wnt signaling. Hum Mol Genet 2008, 17:3105-3117.
106. Saadi-Kheddouci S, Berrebi D, Romagnolo B, Cluzeaud F, Peuchmaur M, Kahn A, Vandewalle A, Perret C. Early development of polycystic kidney disease in transgenic mice expressing an activated mutant of the beta-catenin gene. Oncogene 2001, 20:5972-5981.
107. Miller MM, Iglesias DM, Zhang Z, Corsini R, Chu L, Murawski I, Gupta I, Somlo S, Germino GG, Goodyer PR. T-cell factor/β-catenin activity is suppressed in two different models of autosomal dominant polycystic kidney disease. Kidney Int 2011, 80:146-153.
108. Fischer E, Legue E, Doyen A, Nato F, Nicolas JF, Torres V, Yaniv M, Pontoglio M. Defective planar cell polarity in polycystic kidney disease. Nat Genet 2006, 38:21-23.
109. Simons M, Gloy J, Ganner A, Bullerkotte A, Bashkurov M, Krönig C, Schermer B, Benzing T, Cabello OA, Jenny A. Inversin, the gene product mutated in nephronophthisis type II, functions as a molecular switch between Wnt signaling pathways. Nat Genet 2005, 37:537-543.
110. Belibi FA, Reif G, Wallace DP, Yamaguchi T, Olsen L, Li H, Helmkamp GM Jr, Grantham JJ. Cyclic AMP promotes growth and secretion in human polycystic kidney epithelial cells. Kidney Int 2004, 66:964-973.
111. Calvet JP. Polycystic kidney disease: primary extracellular matrix abnormality or defective cellular differentiation? Kidney Int 1993, 43:101-108.
112. Yamaguchi T, Nagao S, Wallace DP, Belibi FA, Cowley BD, Pelling JC, Grantham JJ. Cyclic AMP activates B-Raf and ERK in cyst epithelial cells from autosomal-dominant polycystic kidneys. Kidney Int 2003, 63:1983-1994.
113. Calvet JP. MEK inhibition holds promise for polycystic kidney disease. J Am Soc Nephrol 2006, 17:1498-1500.
114. Park EY, Sung YH, Yang MH, Noh JY, Park SY, Lee TY, Yook YJ, Yoo KH, Roh KJ, Kim I, et al. Cyst formation in kidney via B-Raf signaling in the PKD2 transgenic mice. J Biol Chem 2009, 284:7214-7222.
115. Magenheimer BS, St John PL, Isom KS, Abrahamson DR, De Lisle RC, Wallace DP, Maser RL, Grantham JJ, Calvet JP. Early embryonic renal tubules of wild-type and polycystic kidney disease kidneys respond to cAMP stimulation with cystic fibrosis transmembrane conductance regulator/Na(+), K(+), 2Cl(-) co-transporter-dependent cystic dilation. J Am Soc Nephrol 2006, 17:3424-3437.
116. Sorenson CM, Padanilam BJ, Hammerman MR. Abnormal postpartum renal development and cystogenesis in the bcl-2 (-/-) mouse. Am J Physiol 1996, 271:F184-F193.
117. Hoetelmans RW, Vahrmeijer AL, van Vlierberghe RL, Keijzer R, van de Velde CJ, Mulder GJ, Van Dierendonck JH. The role of various Bcl-2 domains in the anti-proliferative effect and modulation of cellular glutathione levels: a prominent role for the BH4 domain. Cell Prolif 2003, 36:35-44.
118. Trudel M, D'Agati V, Costantini F. C-myc as an inducer of polycystic kidney disease in transgenic mice. Kidney Int 1991, 39:665-671.
119. Karihaloo A, Koraishy F, Huen SC, Lee Y, Merrick D, Caplan MJ, Somlo S, Cantley LG. Macrophages promote cyst growth in polycystic kidney disease. J Am Soc Nephrol 2011, 22:1809-1814.
120. Swenson-Fields KI, Vivian CJ, Salah SM, Peda JD, Davis BM, van Rooijen N, Wallace DP, Fields TA. Macrophages promote polycystic kidney disease progression. Kidney Int 2013, 83:855-864.
121. Zhou J, Ouyang X, Cui X, Schoeb TR, Smythies LE, Johnson MR, Guay-Woodford LM, Chapman AB, Mrug M. Renal CD14 expression correlates with the progression of cystic kidney disease. Kidney Int 2010, 78:550-560.
122. Vanden Heuvel GB. CD14: a candidate biomarker for the prognosis of polycystic kidney disease. Kidney Int 2010, 78:537-538.
123. Katz SK, Hakki A, Miller AS, Finkelstein SD. Ultrastructural tubular basement membrane lesions in adult polycystic kidney disease. Ann Clin Lab Sci 1989, 19:352-359.
124. Shannon MB, Patton BL, Harvey SJ, Miner JH. A hypomorphic mutation in the mouse laminin alpha5 gene causes polycystic kidney disease. J Am Soc Nephrol 2006, 17:1913-1922.
125. Wallace DP, Quante MT, Reif GA, Nivens E, Ahmed F, Hempson SJ, Blanco G, Yamaguchi T. Periostin induces proliferation of human autosomal dominant polycystic kidney cells through alphaV-integrin receptor. Am J Physiol Renal Physiol 2008, 295:F1463-F1471.
126. Wallace DP, White C, Savinkova L, Nivens E, Reif GA, Pinto CS, Raman A, Parnell SC, Conway SJ, Fields TA. Periostin promotes renal cyst growth and interstitial fibrosis in polycystic kidney disease. Kidney Int 2014, 85:845-854.
127. Lin F, Hiesberger T, Cordes K, Sinclair AM, Goldstein LS, Somlo S, Igarashi P. 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.
128. Nishio S, Tian X, Gallagher AR, Yu Z, Patel V, Igarashi P, Somlo S. Loss of oriented cell division does not initiate cyst formation. J Am Soc Nephrol 2010, 21:295-302.
129. Guay-Woodford LM. Murine models of polycystic kidney disease: molecular and therapeutic insights. Am J Physiol Renal Physiol 2003, 285:F1034-F1049.
130. Belibi FA, Wallace DP, Yamaguchi T, Christensen M, Reif G, Grantham JJ. The effect of caffeine on renal epithelial cells from patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 2002, 13:2723-2729.
131. Laass MW, Spiegel M, Jauch A, Hahn G, Rupprecht E, Vogelberg C, Bartsch O, Huebner A. Tuberous sclerosis and polycystic kidney disease in a 3-month-old infant. Pediatr Nephrol 2004, 19:602-608.
132. Pei Y. Nature and nurture on phenotypic variability of autosomal dominant polycystic kidney disease. Kidney Int 2005, 67:1630-1631.
133. Persu A, Duyme M, Pirson Y, Lens XM, Messiaen T, Breuning MH, Chauveau D, Levy M, Grünfeld JP, Devuyst O. Comparison between siblings and twins supports a role for modifier genes in ADPKD. Kidney Int 2004, 66:2132-2136.
134. Fedeles SV, Tian X, Gallagher AR, Mitobe M, Nishio S, Lee SH, Cai Y, Geng L, Crews CM, Somlo S. A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation. Nat Genet 2011, 43:639-647.
135. Freedman BS, Lam AQ, Sundsbak JL, Iatrino R, Su X, Koon SJ, Wu M, Daheron L, Harris PC, Zhou J, et al. Reduced ciliary polycystin-2 in induced pluripotent stem cells from polycystic kidney disease patients with PKD1 mutations. J Am Soc Nephrol 2013, 24:1571-1586.
136. Pei Y, Lan Z, Wang K, Garcia-Gonzalez M, He N, Dicks E, Parfrey P, Germino G, Watnick T. A missense mutation in PKD1 attenuates the severity of renal disease. Kidney Int 2012, 81:412-417.
137. Happé H, van der Wal AM, Salvatori DC, Leonhard WN, Breuning MH, de Heer E, Peters DJ. Cyst expansion and regression in a mouse model of polycystic kidney disease. Kidney Int 2013, 83:1099-1108.
138. Eccles MR, Stayner CA. Polycystic kidney disease - where gene dosage counts. F1000Prime Rep 2014, 6:24.
139. Ostrom L, Tang MJ, Gruss P, Dressler GR. Reduced Pax2 gene dosage increases apoptosis and slows the progression of renal cystic disease. Dev Biol 2000, 219:250-258.
140. Stayner C, Iglesias DM, Goodyer PR, Ellis L, Germino G, Zhou J, Eccles MR. Pax2 gene dosage influences cystogenesis in autosomal dominant polycystic kidney disease. Hum Mol Genet 2006, 15:3520-3528.
141. Qin S, Taglienti M, Cai L, Zhou J, Kreidberg JA. c-Met and NF-κB-dependent overexpression of Wnt7a and -7b and Pax2 promotes cystogenesis in polycystic kidney disease. J Am Soc Nephrol 2012, 23:1309-1318.
142. Coqueret O, Bérubé G, Nepveu A. The mammalian Cut homeodomain protein functions as a cell-cycle-dependent transcriptional repressor which downmodulates p21WAF1/CIP1/SDI1 in S phase. EMBO J 1998, 17:4680-4694.
143. Ledford AW, Brantley JG, Kemeny G, Foreman TL, Quaggin SE, Igarashi P, Oberhaus SM, Rodova M, Calvet JP, Vanden Heuvel GB. Deregulated expression of the homeobox gene Cux-1 in transgenic mice results in downregulation of p27(kip1) expression during nephrogenesis, glomerular abnormalities, and multiorgan hyperplasia. Dev Biol 2002, 245:157-171.
144. Fero ML, Rivkin M, Tasch M, Porter P, Carow CE, Firpo E, Polyak K, Tsai LH, Broudy V, Perlmutter RM, et al. A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice. Cell 1996, 85:733-744.
145. Kiyokawa H, Kineman RD, Manova-Todorova KO, Soares VC, Hoffman ES, Ono M, Khanam D, Hayday AC, Frohman LA, Koff A. Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27(Kip1). Cell 1996, 85:721-732.
146. Nakayama K, Ishida N, Shirane M, Inomata A, Inoue T, Shishido N, Horii I, Loh DY, Nakayama K. Mice lacking p27(Kip1) display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors. Cell 1996, 85:707-720.
147. Vanden Heuvel GB, Bodmer R, McConnell KR, Nagami GT, Igarashi P. Expression of a cut-related homeobox gene in developing and polycystic mouse kidney. Kidney Int 1996, 50:453-461.
148. Sharma M, Brantley JG, Alcalay NI, Zhou J, Heystek E, Maser RL, Vanden Heuvel GB. Differential expression of Cux-1 and p21 in polycystic kidneys from Pkd1 null and cpk mice. Kidney Int 2005, 67:432-442.
149. Alcalay NI, Sharma M, Vassmer D, Chapman B, Paul B, Zhou J, Brantley JG, Wallace DP, Maser RL, Vanden Heuvel GB. Acceleration of polycystic kidney disease progression in cpk mice carrying a deletion in the homeodomain protein Cux1. Am J Physiol Renal Physiol 2008, 295:F1725-F1734.
150. Patel V, Hajarnis S, Williams D, Hunter R, Huynh D, Igarashi P. MicroRNAs regulate renal tubule maturation through modulation of Pkd1. J Am Soc Nephrol 2012, 23:1941-1948.
151. Patel V, Williams D, Hajarnis S, Hunter R, Pontoglio M, Somlo S, Igarashi P. miR-17∼92 miRNA cluster promotes kidney cyst growth in polycystic kidney disease. Proc Natl Acad Sci USA 2013, 110:10765-10770.
152. Wang E, Hsieh-Li HM, Chiou YY, Chien YL, Ho HH, Chin HJ, Wang CK, Liang SC, Jiang ST. Progressive renal distortion by multiple cysts in transgenic mice expressing artificial microRNAs against Pkd1. J Pathol 2010, 222:238-248.
153. Menezes LF, Zhou F, Patterson AD, Piontek KB, Krausz KW, Gonzalez FJ, Germino GG. Network analysis of a Pkd1-mouse model of autosomal dominant polycystic kidney disease identifies HNF4α as a disease modifier. PLoS Genet 2012, 8:e1003053.
154. Tran PV, Sharma M, Li X, Calvet JP. Developmental signaling: does it bridge the gap between cilia dysfunction and renal cystogenesis? Birth Defects Res C Embryo Today 2014, 102:159-173.
155. Prasad S, McDaid JP, Tam FW, Haylor JL, Ong AC. Pkd2 dosage influences cellular repair responses following ischemia-reperfusion injury. Am J Pathol 2009, 175:1493-1503.