Digestive and Liver Disease
Volume 42, Issue 4 , Pages 261-271 , April 2010

Polycystic liver diseases

  • P. Onori

      Affiliations

    • Experimental Medicine, University of L’Aquila, L’Aquila, Italy
  • ,
  • A. Franchitto

      Affiliations

    • Dept Human Anatomy, University of Rome “La Sapienza”, Rome, Italy
  • ,
  • R. Mancinelli

      Affiliations

    • Dept Human Anatomy, University of Rome “La Sapienza”, Rome, Italy
  • ,
  • G. Carpino

      Affiliations

    • Dept Health Science, University of Rome “Foro Italico”, Italy
  • ,
  • D. Alvaro

      Affiliations

    • Gastroenterology, Polo Pontino, University of Rome “La Sapienza”, Rome, Italy
  • ,
  • H. Francis

      Affiliations

    • Research, Central Texas Veterans Health Care System, USA
  • ,
  • G. Alpini

      Affiliations

    • Research, Central Texas Veterans Health Care System, USA
    • Scott & White Digestive Disease Research Center, Texas A&M Health Science Center, College of Medicine, USA
  • ,
  • E. Gaudio

      Affiliations

    • Dept Human Anatomy, University of Rome “La Sapienza”, Rome, Italy
    • Corresponding Author InformationCorresponding author. Tel.: +39 0649918060; fax: +39 0649918062.

Received 23 November 2009 ,Accepted 7 January 2010.

References 

  1. Everson GT, Helmke SM, Doctor B. Advances in management of polycystic liver disease. Expert Rev Gastroenterol Hepatol. 2008;2:563–576
  2. Masyuk T, LaRusso N. Polycystic liver disease: new insights into disease pathogenesis. Hepatology. 2006;43:906–908
  3. Everson GT, Taylor MR, Doctor RB. Polycystic disease of the liver. Hepatology. 2004;40:774–782
  4. Torres VE, Harris PC, Pirson Y. Autosomal dominant polycystic kidney disease. Lancet. 2007;369:1287–1301
  5. Xu C, Rossetti S, Jiang L, et al. Human ADPKD primary cyst epithelial cells with a novel, single codon deletion in the PKD1 gene exhibit defective ciliary polycystin localization and loss of flow-induced Ca2+ signaling. Am J Physiol Renal Physiol. 2007;292:F930–F945
  6. Everson GT. Hepatic cysts in autosomal dominant polycystic kidney disease. Mayo Clin Proc. 1990;65:1020–1025
  7. Grunfeld JP, Albouze G, Jungers P, et al. Liver changes and complications in adult polycystic kidney disease. Adv Nephrol Necker Hosp. 1985;14:1–20
  8. Gabow PA, Johnson AM, Kaehny WD, et al. Risk factors for the development of hepatic cysts in autosomal dominant polycystic kidney disease. Hepatology. 1990;11:1033–1037
  9. Newman KD, Torres VE, Rakela J, et al. Treatment of highly symptomatic polycystic liver disease. Preliminary experience with a combined hepatic resection–fenestration procedure. Ann Surg. 1990;212:30–37
  10. Sessa A, Meroni M, Righetti M, et al. Autosomal recessive polycystic kidney disease. Contrib Nephrol. 2001;50–56
  11. Shneider BL, Magid MS. Liver disease in autosomal recessive polycystic kidney disease. Pediatr Transpl. 2005;9:634–639
  12. Onuchic LF, Furu L, Nagasawa Y, et al. PKHD1, the polycystic kidney and hepatic disease 1 gene, encodes a novel large protein containing multiple immunoglobulin-like plexin-transcription-factor domains and parallel beta-helix 1 repeats. Am J Hum Genet. 2002;70:1305–1317
  13. Ward CJ, Hogan MC, Rossetti S, et al. The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein. Nat Genet. 2002;30:259–269
  14. Roy S, Dillon MJ, Trompeter RS, et al. Autosomal recessive polycystic kidney disease: long-term outcome of neonatal survivors. Pediatr Nephrol. 1997;11:302–306
  15. Guay-Woodford LM, Desmond RA. Autosomal recessive polycystic kidney disease: the clinical experience in North America. Pediatrics. 2003;111:1072–1080
  16. Lilova MI, Petkov DL. Intracranial aneurysms in a child with autosomal recessive polycystic kidney disease. Pediatr Nephrol. 2001;16:1030–1032
  17. Yonemura K, Yasuda H, Fujigaki Y, et al. Adrenal insufficiency due to isolated adrenocorticotropin deficiency complicated by autosomal recessive polycystic kidney disease. Ren Fail. 2003;25:485–492
  18. Bae KT, Zhu F, Chapman AB, et al. Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease cohort. Clin J Am Soc Nephrol. 2006;1:64–69
  19. Bleeker-Rovers CP, Vos FJ, Corstens FH, et al. Imaging of infectious diseases using [18F] fluorodeoxyglucose PET. Q J Nucl Med Mol Imaging. 2008;52:17–29
  20. Drenth JP, Martina JA, Te Morsche RH, et al. Molecular characterization of hepatocystin, the protein that is defective in autosomal dominant polycystic liver disease. Gastroenterology. 2004;126:1819–1827
  21. Torres VE, Harris PC. Autosomal dominant polycystic kidney disease: the last 3 years. Kidney Int. 2009;76:149–168
  22. Masyuk T, Masyuk A, LaRusso N. Cholangiociliopathies: genetics, molecular mechanisms and potential therapies. Curr Opin Gastroenterol. 2009;25:265–271
  23. Fencl F, Janda J, Blahova K, et al. Genotype–phenotype correlation in children with autosomal dominant polycystic kidney disease. Pediatr Nephrol. 2009;24:983–989
  24. Tahvanainen E, Tahvanainen P, Kaariainen H, et al. Polycystic liver and kidney diseases. Ann Med. 2005;37:546–555
  25. Ibraghimov-Beskrovnaya O, Bukanov N. Polycystic kidney diseases: from molecular discoveries to targeted therapeutic strategies. Cell Mol Life Sci. 2008;65:605–619
  26. Hughes J, Ward CJ, Peral B, et al. The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains. Nat Genet. 1995;10:151–160
  27. Newby LJ, Streets AJ, Zhao Y, et al. Identification, characterization, and localization of a novel kidney polycystin-1–polycystin-2 complex. J Biol Chem. 2002;277:20763–20773
  28. Streets AJ, Newby LJ, O’Hare MJ, et al. Functional analysis of PKD1 transgenic lines reveals a direct role for polycystin-1 in mediating cell–cell adhesion. J Am Soc Nephrol. 2003;14:1804–1815
  29. Qian F, Wei W, Germino G, et al. The nanomechanics of polycystin-1 extracellular region. J Biol Chem. 2005;280:40723–40730
  30. Ong AC, Harris PC. Molecular pathogenesis of ADPKD: the polycystin complex gets complex. Kidney Int. 2005;67:1234–1247
  31. Giamarchi A, Padilla F, Coste B, et al. The versatile nature of the calcium-permeable cation channel TRPP2. EMBO Rep. 2006;7:787–793
  32. Streets AJ, Moon DJ, Kane ME, et al. Identification of an N-terminal glycogen synthase kinase 3 phosphorylation site which regulates the functional localization of polycystin-2 in vivo and in vitro. Hum Mol Genet. 2006;15:1465–1473
  33. Qian Q, Li A, King BF, et al. Clinical profile of autosomal dominant polycystic liver disease. Hepatology. 2003;37:164–171
  34. Lazaridis KN, Strazzabosco M, LaRusso NF. The cholangiopathies: disorders of biliary epithelia. Gastroenterology. 2004;127:1565–1577
  35. Drenth JP, te Morsche RH, Smink R, et al. Germline mutations in PRKCSH are associated with autosomal dominant polycystic liver disease. Nat Genet. 2003;33:345–347
  36. Davila S, Furu L, Gharavi AG, et al. Mutations in SEC63 cause autosomal dominant polycystic liver disease. Nat Genet. 2004;36:575–577
  37. Drenth JP, Martina JA, van de Kerkhof R, et al. Polycystic liver disease is a disorder of cotranslational protein processing. Trends Mol Med. 2005;11:37–42
  38. Bergmann C, Frank V, Kupper F, et al. Functional analysis of PKHD1 splicing in autosomal recessive polycystic kidney disease. J Hum Genet. 2006;51:788–793
  39. Bork P, Doerks T, Springer TA, et al. Domains in plexins: links to integrins and transcription factors. Trends Biochem Sci. 1999;24:261–263
  40. Hogan MC, Griffin MD, Rossetti S, et al. PKHDL1, a homolog of the autosomal recessive polycystic kidney disease gene, encodes a receptor with inducible T lymphocyte expression. Hum Mol Genet. 2003;12:685–698
  41. Wang S, Luo Y, Wilson PD, et al. The autosomal recessive polycystic kidney disease protein is localized to primary cilia, with concentration in the basal body area. J Am Soc Nephrol. 2004;15:592–602
  42. Zhang MZ, Mai W, Li C, et al. PKHD1 protein encoded by the gene for autosomal recessive polycystic kidney disease associates with basal bodies and primary cilia in renal epithelial cells. Proc Natl Acad Sci USA. 2004;101:2311–2316
  43. Wheatley DN. Primary cilia in normal and pathological tissues. Pathobiology. 1995;63:222–238
  44. Praetorius HA, Spring KR. A physiological view of the primary cilium. Annu Rev Physiol. 2005;67:515–529
  45. Davenport JR, Yoder BK. An incredible decade for the primary cilium: a look at a once-forgotten organelle. Am J Physiol Renal Physiol. 2005;289:F1159–F1169
  46. Masyuk AI, Masyuk TV, LaRusso NF. Cholangiocyte primary cilia in liver health and disease. Dev Dyn. 2008;237:2007–2012
  47. Huang BQ, Masyuk TV, Muff MA, et al. Isolation and characterization of cholangiocyte primary cilia. Am J Physiol Gastrointest Liver Physiol. 2006;291:G500–G509
  48. Christensen ST, Pedersen LB, Schneider L, et al. Sensory cilia and integration of signal transduction in human health and disease. Traffic. 2007;8:97–109
  49. Satir P, Christensen ST. Overview of structure and function of mammalian cilia. Annu Rev Physiol. 2007;69:377–400
  50. Masyuk AI, Masyuk TV, Splinter PL, et al. Cholangiocyte cilia detect changes in luminal fluid flow and transmit them into intracellular Ca2+ and cAMP signaling. Gastroenterology. 2006;131:911–920
  51. Muchatuta MN, Gattone VH, Witzmann FA, et al. Structural and functional analyses of liver cysts from the BALB/c-cpk mouse model of polycystic kidney disease. Exp Biol Med (Maywood). 2009;234:17–27
  52. Yost HJ. Left-right asymmetry: nodal cilia make and catch a wave. Curr Biol. 2003;13:R808–R809
  53. Pazour GJ, San Agustin JT, Follit JA, 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
  54. 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
  55. Pan J, Wang Q, Snell WJ. Cilium-generated signaling and cilia-related disorders. Lab Invest. 2005;85:452–463
  56. Vogel G. News focus: betting on cilia. Science. 2005;310:216–218
  57. Torrice A, Cardinale V, Gatto M, et al. Polycystins play a key role in the modulation of cholangiocyte proliferation. Dig Liver Dis; doi:10.1016/j.dld.2009.09.008.
  58. Liu W, Xu S, Woda C, et al. Effect of flow and stretch on the [Ca2+]i response of principal and intercalated cells in cortical collecting duct. Am J Physiol Renal Physiol. 2003;285:F998–F1012
  59. Liu W, Murcia NS, Duan Y, et al. Mechanoregulation of intracellular Ca2+ concentration is attenuated in collecting duct of monocilium-impaired orpk mice. Am J Physiol Renal Physiol. 2005;289:F978–F988
  60. Praetorius HA, Spring KR. Bending the MDCK cell primary cilium increases intracellular calcium. J Membr Biol. 2001;184:71–79
  61. Praetorius HA, Spring KR. Removal of the MDCK cell primary cilium abolishes flow sensing. J Membr Biol. 2003;191:69–76
  62. Fliegauf M, Benzing T, Omran H. When cilia go bad: cilia defects and ciliopathies. Nat Rev Mol Cell Biol. 2007;8:880–893
  63. Alpini G, Phinizy JL, Glaser S, et al. Development and characterization of secretin-stimulated secretion of cultured rat cholangiocytes. Am J Physiol Gastrointest Liver Physiol. 2003;284:G1066–G1073
  64. Alpini G, Glaser S, Alvaro D, et al. Bile acid depletion and repletion regulate cholangiocyte growth and secretion by a phosphatidylinositol 3-kinase-dependent pathway in rats. Gastroenterology. 2002;123:1226–1237
  65. Alpini G, Glaser SS, Rodgers R, et al. Functional expression of the apical Na+-dependent bile acid transporter in large but not small rat cholangiocytes. Gastroenterology. 1997;113:1734–1740
  66. Masyuk AI, Gong AY, Kip S, et al. Perfused rat intrahepatic bile ducts secrete and absorb water, solute, and ions. Gastroenterology. 2000;119:1672–1680
  67. Splinter PL, Masyuk AI, LaRusso NF. Specific inhibition of AQP1 water channels in isolated rat intrahepatic bile duct units by small interfering RNAs. J Biol Chem. 2003;278:6268–6274
  68. Yoder BK. Role of primary cilia in the pathogenesis of polycystic kidney disease. J Am Soc Nephrol. 2007;18:1381–1388
  69. Alvaro D, Onori P, Alpini G, et al. Morphological and functional features of hepatic cyst epithelium in autosomal dominant polycystic kidney disease. Am J Pathol. 2008;172:321–332
  70. Calvet JP. Molecular genetics of polycystic kidney disease. J Nephrol. 1998;11:24–34
  71. Parker E, Newby LJ, Sharpe CC, et al. Hyperproliferation of PKD1 cystic cells is induced by insulin-like growth factor-1 activation of the Ras/Raf signalling system. Kidney Int. 2007;72:157–165
  72. Grantham JJ, Ye M, Gattone VH. In vitro fluid secretion by epithelium from polycystic kidneys. J Clin Invest. 1995;95:195–202
  73. Motta PM. The three-dimensional microanatomy of the liver. Arch Histol Jpn. 1984;47:1–30
  74. Torres VE, Harris PC. Mechanisms of disease: autosomal dominant and recessive polycystic kidney diseases. Nat Clin Pract Nephrol. 2006;2:40–55[quiz 55]
  75. Qian F, Watnick TJ, Onuchic LF, et al. The molecular basis of focal cyst formation in human autosomal dominant polycystic kidney disease type I. Cell. 1996;87:979–987
  76. Wu G, D’Agati V, Cai Y, et al. Somatic inactivation of Pkd2 results in polycystic kidney disease. Cell. 1998;93:177–188
  77. Colgin LM, Hackmann AF, Emond MJ, et al. The unexpected landscape of in vivo somatic mutation in a human epithelial cell lineage. Proc Natl Acad Sci USA. 2002;99:1437–1442
  78. 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 Invest. 2005;115:910–918
  79. Guay-Woodford LM. Murine models of polycystic kidney disease: molecular and therapeutic insights. Am J Physiol Renal Physiol. 2003;285:F1034–F1049
  80. Sanzen T, Harada K, Yasoshima M, et al. Polycystic kidney rat is a novel animal model of Caroli's disease associated with congenital hepatic fibrosis. Am J Pathol. 2001;158:1605–1612
  81. Fry JL, Koch WE, Jennette JC, et al. A genetically determined murine model of infantile polycystic kidney disease. J Urol. 1985;134:828–833
  82. Nauta J, Ozawa Y, Sweeney WE, et al. Renal and biliary abnormalities in a new murine model of autosomal recessive polycystic kidney disease. Pediatr Nephrol. 1993;7:163–172
  83. Muto S, Aiba A, Saito Y, et al. Pioglitazone improves the phenotype and molecular defects of a targeted Pkd1 mutant. Hum Mol Genet. 2002;11:1731–1742
  84. Pennekamp P, Karcher C, Fischer A, et al. The ion channel polycystin-2 is required for left-right axis determination in mice. Curr Biol. 2002;12:938–943
  85. Gretz N, Kranzlin B, Pey R, et al. Rat models of autosomal dominant polycystic kidney disease. Nephrol Dial Transpl. 1996;11(Suppl. 6):46–51
  86. Nauta J, Goedbloed MA, Herck HV, et al. New rat model that phenotypically resembles autosomal recessive polycystic kidney disease. J Am Soc Nephrol. 2000;11:2272–2284
  87. Lubarsky B, Krasnow MA. Tube morphogenesis: making and shaping biological tubes. Cell. 2003;112:19–28
  88. Muff MA, Masyuk TV, Stroope AJ, et al. Development and characterization of a cholangiocyte cell line from the PCK rat, an animal model of Autosomal Recessive Polycystic Kidney Disease. Lab Invest. 2006;86:940–950
  89. Perrone RD, Grubman SA, Rogers LC, et al. Continuous epithelial cell lines from ADPKD liver cysts exhibit characteristics of intrahepatic biliary epithelium. Am J Physiol Gastrointest Live Physiol. 1995;269:G335–G345
  90. Perrone RD, Grubman SA, Murray SL, et al. Autosomal dominant polycystic kidney disease decreases anion exchanger activity. Am J Physiol Gastrointest Live Physiol. 1997;272:C1748–C1756
  91. Bello-Reuss E, Holubec K, Rajaraman S. Angiogenesis in autosomal-dominant polycystic kidney disease. Kidney Int. 2001;60:37–45
  92. Jakkula M, Le Cras TD, Gebb S, et al. Inhibition of angiogenesis decreases alveolarization in the developing rat lung. Am J Physiol Lung Cell Mol Physiol. 2000;279:L600-7
  93. Brodsky KS, McWilliams RR, Amura CR, et al. Liver cyst cytokines promote endothelial cell proliferation and development. Exp Biol Med (Maywood). 2009;234:1155–1165
  94. Gaudio E, Barbaro B, Alvaro D, et al. Administration of r-VEGF-A prevents hepatic artery ligation-induced bile duct damage in bile duct ligated rats. Am J Physiol Gastrointest Liver Physiol. 2006;291:G307–G317
  95. Gaudio E, Barbaro B, Alvaro D, et al. Vascular endothelial growth factor stimulates rat cholangiocyte proliferation via an autocrine mechanism. Gastroenterology. 2006;130:1270–1282
  96. Amura CR, Brodsky KS, Groff R, et al. VEGF receptor inhibition blocks liver cyst growth in pkd2(WS25/-) mice. Am J Physiol Cell Physiol. 2007;293:C419–C428
  97. Fabris L, Cadamuro M, Fiorotto R, et al. Effects of angiogenic factor overexpression by human and rodent cholangiocytes in polycystic liver diseases. Hepatology. 2006;43:1001–1012
  98. Gaudio E, Franchitto A, Pannarale L, et al. Cholangiocytes and blood supply. World J Gastroenterol. 2006;12:3546–3552
  99. Mancinelli R, Onori P, Gaudio E, et al. Taurocholate feeding to bile duct ligated rats prevents caffeic acid-induced bile duct damage by changes in cholangiocyte VEGF expression. Exp Biol Med (Maywood). 2009;234:462–474
  100. Ross MA, Sander CM, Kleeb TB, et al. Spatiotemporal expression of angiogenesis growth factor receptors during the revascularization of regenerating rat liver. Hepatology. 2001;34:1135–1148
  101. Spirli C, Okolicsanyi S, Fiorotto R, et al. ERK1/2-dependent vascular endothelial growth factor signaling sustains cyst growth in polycystin-2 defective mice. Gastroenterology. 2009;
  102. Fabris L, Strazzabosco M, Crosby HA, et al. Characterization and isolation of ductular cells coexpressing neural cell adhesion molecule and Bcl-2 from primary cholangiopathies and ductal plate malformations. Am J Pathol. 2000;156:1599–1612
  103. Masyuk TV, Huang BQ, Ward CJ, et al. Defects in cholangiocyte fibrocystin expression and ciliary structure in the PCK rat. Gastroenterology. 2003;125:1303–1310
  104. Wilson PD. Polycystin: new aspects of structure, function, and regulation. J Am Soc Nephrol. 2001;12:834–845
  105. Yamaguchi T, Hempson SJ, Reif GA, et al. Calcium restores a normal proliferation phenotype in human polycystic kidney disease epithelial cells. J Am Soc Nephrol. 2006;17:178–187
  106. Yamaguchi T, Wallace DP, Magenheimer BS, et al. Calcium restriction allows cAMP activation of the B-Raf/ERK pathway, switching cells to a cAMP-dependent growth-stimulated phenotype. J Biol Chem. 2004;279:40419–40430
  107. Glaser SS, Gaudio E, Miller T, et al. Cholangiocyte proliferation and liver fibrosis. Expert Rev Mol Med. 2009;11:e7
  108. Alpini G, Ueno Y, Glaser SS, et al. Bile acid feeding increased proliferative activity and apical bile acid transporter expression in both small and large rat cholangiocytes. Hepatology. 2001;34:868–876
  109. Alpini G, Glaser SS, Ueno Y, et al. Bile acid feeding induces cholangiocyte proliferation and secretion: evidence for bile acid-regulated ductal secretion. Gastroenterology. 1999;116:179–186
  110. Masyuk TV, Masyuk AI, Torres VE, et al. Octreotide inhibits hepatic cystogenesis in a rodent model of polycystic liver disease by reducing cholangiocyte adenosine 3′,5′-cyclic monophosphate. Gastroenterology. 2007;132:1104–1116
  111. Banales JM, Prieto J, Medina JF. Cholangiocyte anion exchange and biliary bicarbonate excretion. World J Gastroenterol. 2006;12:3496–3511
  112. Wang S, Zhang J, Nauli SM, et al. Fibrocystin/polyductin, found in the same protein complex with polycystin-2, regulates calcium responses in kidney epithelia. Mol Cell Biol. 2007;27:3241–3252
  113. Gradilone SA, Masyuk AI, Splinter PL, et al. Cholangiocyte cilia express TRPV4 and detect changes in luminal tonicity inducing bicarbonate secretion. Proc Natl Acad Sci USA. 2007;104:19138–19143
  114. Banales JM, Masyuk TV, Gradilone SA, et al. The cAMP effectors Epac and protein kinase a (PKA) are involved in the hepatic cystogenesis of an animal model of autosomal recessive polycystic kidney disease (ARPKD). Hepatology. 2009;49:160–174
  115. Amura CR, Brodsky KS, Gitomer B, et al. CXCR2 agonists in ADPKD liver cyst fluids promote cell proliferation. Am J Physiol Cell Physiol. 2008;294:C786–C796
  116. Lai X, Blazer-Yost BL, Gattone VH, 2nd , et al. Protein composition of liver cyst fluid from the BALB/c-cpk/+ mouse model of autosomal recessive polycystic kidney disease. Proteomics. 2009;9:3775–3782
  117. Mitsuyama K, Toyonaga A, Sasaki E, et al. IL-8 as an important chemoattractant for neutrophils in ulcerative colitis and Crohn's disease. Clin Exp Immunol. 1994;96:432–436
  118. Addison CL, Daniel TO, Burdick MD, et al. The CXC chemokine receptor 2, CXCR2, is the putative receptor for ELR+ CXC chemokine-induced angiogenic activity. J Immunol. 2000;165:5269–5277
  119. Wang Y, Yang J, Gao Y, et al. Regulatory effect of e2, IL-6 and IL-8 on the growth of epithelial ovarian cancer cells. Cell Mol Immunol. 2005;2:365–372
  120. Alvaro D, Metalli VD, Alpini G, et al. The intrahepatic biliary epithelium is a target of the growth hormone/insulin-like growth factor 1 axis. J Hepatol. 2005;43:875–883
  121. Alvaro D, Alpini G, Onori P, et al. Estrogens stimulate proliferation of intrahepatic biliary epithelium in rats. Gastroenterology. 2000;119:1681–1691
  122. Alvaro D, Macarri G, Mancino MG, et al. Serum and biliary insulin-like growth factor I and vascular endothelial growth factor in determining the cause of obstructive cholestasis. Ann Intern Med. 2007;147:451–459
  123. Onori P, Alvaro D, Floreani AR, et al. Activation of the IGF1 system characterizes cholangiocyte survival during progression of primary biliary cirrhosis. J Histochem Cytochem. 2007;55:327–334
  124. Koduri S, Goldhar AS, Vonderhaar BK. Activation of vascular endothelial growth factor (VEGF) by the ER-alpha variant, ERDelta3. Breast Cancer Res Treat. 2006;95:37–43
  125. Chapman AB. Cystic disease in women: clinical characteristics and medical management. Adv Ren Replace Ther. 2003;10:24–30
  126. Sherstha R, McKinley C, Russ P, et al. Postmenopausal estrogen therapy selectively stimulates hepatic enlargement in women with autosomal dominant polycystic kidney disease. Hepatology. 1997;26:1282–1286
  127. Bogovich K. Follicle-stimulating hormone plays a role in the induction of ovarian follicular cysts in hypophysectomized rats. Biol Reprod. 1992;47:149–161
  128. Surmacz E. Growth factor receptors as therapeutic targets: strategies to inhibit the insulin-like growth factor I receptor. Oncogene. 2003;22:6589–6597
  129. Mancinelli R, Onori P, Gaudio E, et al. Follicle-stimulating hormone increases cholangiocyte proliferation by an autocrine mechanism via cAMP-dependent phosphorylation of ERK1/2 and Elk-1. Am J Physiol Gastrointest Liver Physiol. 2009;297:G11–26
  130. Karlsson-Rosenthal C, Millar JB. Cdc25: mechanisms of checkpoint inhibition and recovery. Trends Cell Biol. 2006;16:285–292
  131. Masyuk T, Masyuk A, LaRusso N. MicroRNAs in cholangiociliopathies. Cell Cycle. 2009;8:1324–1328
  132. 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;17:2220–2227
  133. 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
  134. Keimpema LV, Nevens F, Vanslembrouck R, et al. Lanreotide reduces the volume of polycystic liver: A randomized, double-blind, placebo-controlled trial. Gastroenterology. 2009;

PII: S1590-8658(10)00010-1

doi: 10.1016/j.dld.2010.01.006

Digestive and Liver Disease
Volume 42, Issue 4 , Pages 261-271 , April 2010