Abstract
Autosomal-dominant polycystic kidney disease (ADPKD) is a common hereditary disease that features multiple cystogenesis in various organs and vascular defects. The genes responsible for ADPKD, PKD1, and PKD2 have been identified, and the pathological processes of the disease are becoming clearer. This review focuses on recent findings about the molecular and cellular biology of ADPKD, and especially on PKD1. PKD1 and its product, polycystin-1, play pivotal roles in cellular differentiation because they regulate the cell cycle and because polycystin-1 is a component of adherens junctions. A possible link between polycystin-1 and PPARγ is discussed. The extraordinarily fast research progress in this area in the last decade has now reached a stage where the development of a remedy for ADPKD might become possible in the near future.
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References
E Higashihara K Nutahara M Kojima A Tamakoshi O Yoshiyuki H Sakai et al. (1998) ArticleTitlePrevalence and renal prognosis of diagnosed autosomal-dominant polycystic kidney disease in Japan Nephron 80 421–7 Occurrence Handle1:STN:280:DyaK1M%2FlsVyjug%3D%3D Occurrence Handle9832641 Occurrence Handle10.1159/000045214
E Higashihara Y Aso J Shimazaki et al. (1992) ArticleTitleClinical aspects of polycystic kidney disease J Urol 147 329–32 Occurrence Handle1:STN:280:DyaK387it1emug%3D%3D Occurrence Handle1732586 Occurrence Handle10.1016/S0022-5347(17)37228-2
JJ Grantham (1993) ArticleTitleFluid secretion, cellular proliferation, and the pathogenesis of renal epithelial cysts J Am Soc Nephrol 3 1843–57
AB Chapman RW Schrier (1991) ArticleTitlePathogenesis of hypertension in autosomal-dominant polycystic kidney disease Semin Nephrol 11 653–60 Occurrence Handle1:STN:280:DyaK387hsF2quw%3D%3D Occurrence Handle1767138
VE Torres Y Cai X Chen GQ Wu L Geng KA Cleghorn et al. (2001) ArticleTitleVascular expression of polycystin-2 J Am Soc Nephrol 12 1–9 Occurrence Handle1:CAS:528:DC%2BD3MXkvFGrtQ%3D%3D Occurrence Handle11134244
AB Chapman AM Johnson S Rainguet et al. (1997) ArticleTitleLeft ventricular hypertrophy in autosomal-dominant polycystic kidney disease J Am Soc Nephrol 8 1292 Occurrence Handle1:STN:280:DyaK2svgt1aqsA%3D%3D Occurrence Handle9259356
L Mariani MG Bianchetti G Schroth et al. (1999) ArticleTitleCerebral aneurysms in patients with autosomal-dominant polycystic kidney disease – to screen, to clip, to coil? Nephrol Dial Transplant 14 2319–22 Occurrence Handle1:STN:280:DyaK1MvlsF2hsg%3D%3D Occurrence Handle10528652 Occurrence Handle10.1093/ndt/14.10.2319
VE Torres (1999) ArticleTitleExtrarenal manifestations of autosomal-dominant polycystic kidney disease Am J Kidney Dis 34 xlv–xlviii Occurrence Handle1:STN:280:DC%2BD3c%2FnsFGmsw%3D%3D Occurrence Handle10585334 Occurrence Handle10.1016/S0272-6386(99)70001-6
International Polycystic (1994) ArticleTitleKidney Disease Consortium. The polycystic kidney disease 1 gene encodes a 14-kb transcript and lies within a duplicated region on chromosome 16 Cell 77 881–94 Occurrence Handle10.1016/0092-8674(94)90137-6
T Mochizuki G Wu T Hayashi SL Xenophontos B Veldhuisen JJ Saris et al. (1996) ArticleTitlePKD2, a gene for polycystic kidney disease that encodes an integral membrane protein Science 272 1339–42 Occurrence Handle1:CAS:528:DyaK28Xjt1Okurk%3D Occurrence Handle8650545 Occurrence Handle10.1126/science.272.5266.1339
N Hateboer MA v Dijk N Bogdanova E Coto AK Saggar-Malik JL San Millan et al. (1999) ArticleTitleComparison of phenotypes of polycystic kidney disease types 1 and 2 Lancet 353 103–7 Occurrence Handle1:STN:280:DyaK1M7ks1Gjsg%3D%3D Occurrence Handle10023895 Occurrence Handle10.1016/S0140-6736(98)03495-3
J Hughes CJ Ward B Peral R Aspinwall K Clark JL San Millan et al. (1995) ArticleTitleThe polycystic kidney disease1 (PKD1) gene encodes a novel protein with multiple cell recognition domains Nat Genet 10 151–9 Occurrence Handle1:CAS:528:DyaK2MXmtFCqtrg%3D Occurrence Handle7663510 Occurrence Handle10.1038/ng0695-151
N Bogdanova A Markoff V Gerke M McCluskey J Horst B Dworniczak (2001) ArticleTitleHomologues to the first gene for autosomal-dominant polycystic kidney disease are pseudogenes Genomics 74 333–41 Occurrence Handle1:CAS:528:DC%2BD3MXksVChsLY%3D Occurrence Handle11414761 Occurrence Handle10.1006/geno.2001.6568
S Rossetti L Strmecki V Gamble S Burton V Sneddon B Peral et al. (2001) ArticleTitleMutation analysis of the entire PKD1 gene: genetic and diagnostic implications Am J Hum Genet 68 46–63 Occurrence Handle1:CAS:528:DC%2BD3MXnt1ehsA%3D%3D Occurrence Handle11115377 Occurrence Handle10.1086/316939
B Phakdeekitcharoen TJ Watnick GG Germino (2001) ArticleTitleMutation analysis of the entire replicated portion of PKD1 using genomic DNA samples J Am Soc Nephrol 12 955–63 Occurrence Handle1:CAS:528:DC%2BD3MXjvVCgtLo%3D Occurrence Handle11316854
S Rossetti D Chauveau D Walker A Saggar-Malik CG Winearls VE Torres et al. (2002) ArticleTitleA complete mutation screen of the ADPKD genes by DHPLC Kidney Int 61 1588–99 Occurrence Handle1:CAS:528:DC%2BD38XjvFWiu74%3D Occurrence Handle11967008 Occurrence Handle10.1046/j.1523-1755.2002.00326.x
PC Harris (1999) ArticleTitleAutosomal-dominant polycystic kidney disease: clues to pathogenesis Hum Mol Genet 8 1861–6 Occurrence Handle1:CAS:528:DyaK1MXmslemu7s%3D Occurrence Handle10469838 Occurrence Handle10.1093/hmg/8.10.1861
S Rossetti S Burton L Strmecki GR Pond JL San Millan K Zerres et al. (2002) ArticleTitleThe position of the polycystic kidney disease 1 (PKD1) gene mutation correlates with the severity of renal disease J Am Soc Nephrol 13 1230–7 Occurrence Handle1:CAS:528:DC%2BD38XktFaisbc%3D Occurrence Handle11961010 Occurrence Handle10.1097/01.ASN.0000013300.11876.37
S Rossetti D Chauveau V Kubly JM Slezak AK Saggar-Malik Y Pei et al. (2003) ArticleTitleAssociation of mutation position in polycystic kidney disease 1 (PKD1) gene and development of a vascular phenotype Lancet 361 2196–201 Occurrence Handle1:CAS:528:DC%2BD3sXkvFelsbg%3D Occurrence Handle12842373 Occurrence Handle10.1016/S0140-6736(03)13773-7
Y Pei N He K Wang et al. (1998) ArticleTitleA spectrum of mutations in the polycystic kidney disease-2 (PKD2) gene from eight Canadian kindreds J Am Soc Nephrol 9 1853–60 Occurrence Handle1:STN:280:DyaK1cvksVOksg%3D%3D Occurrence Handle9773786
JL Brasier EP Henske (1997) ArticleTitleLoss of the polycystic kidney disease (PKD1) region of chromosome 16p13 in renal cyst cells supports a loss-of-function model for cyst pathogenesis J Clin Invest 99 194–9 Occurrence Handle1:CAS:528:DyaK2sXntVKjsA%3D%3D Occurrence Handle9005987 Occurrence Handle507786 Occurrence Handle10.1172/JCI119147
M Koptides C Hadjimichael P Koupepidou A Pierides CC Deltas (1999) ArticleTitleGerminal and somatic mutations in the PKD2 gene of renal cysts in autosomal-dominant polycystic kidney disease Hum Mol Genet 8 509–13 Occurrence Handle1:CAS:528:DyaK1MXhslKltL0%3D Occurrence Handle9949210 Occurrence Handle10.1093/hmg/8.3.509
TJ Watnick VE Torres MA Gandolph F Qian LF Onuchic KW Klinger et al. (1998) ArticleTitleSomatic mutation in individual liver cysts supports a two-hit model of cystogenesis in autosomal-dominant polycystic kidney disease Mol Cell 2 247–51 Occurrence Handle1:CAS:528:DyaK1cXmtVyisrs%3D Occurrence Handle9734362 Occurrence Handle10.1016/S1097-2765(00)80135-5
Y Pei TJ Watnick N He K Wang Y Liang P Parfrey et al. (1999) ArticleTitleSomatic PKD2 mutations in individual kidney and liver cysts support a “two-hit” model of cystogenesis in type 2 autosomal-dominant polycystic kidney disease J Am Soc Nephrol 10 1524–9 Occurrence Handle1:CAS:528:DyaK1MXktlKhurk%3D Occurrence Handle10405208
LM Colgin AFM Hackmann MJ Emond RJ Monnat SuffixJr (2002) ArticleTitleThe unexpected landscape of in vivo somatic mutation in a human epithelial cell lineage Proc Natl Acad Sci USA 99 1437–42 Occurrence Handle1:CAS:528:DC%2BD38Xht1ClsL0%3D Occurrence Handle11818556 Occurrence Handle122209 Occurrence Handle10.1073/pnas.032655699
P Igarashi S Somlo (2002) ArticleTitleGenetics and pathogenesis of polycystic kidney disease J Am Soc Nephrol 13 2384–98 Occurrence Handle1:CAS:528:DC%2BD38XntlSrurY%3D Occurrence Handle12191984 Occurrence Handle10.1097/01.ASN.0000028643.17901.42
NA Bhowmick A Chytil D Plieth AE Gorska N Dumont S Shappell et al. (2004) ArticleTitleTGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia Science 303 848–51 Occurrence Handle1:CAS:528:DC%2BD2cXovVKmtQ%3D%3D Occurrence Handle14764882 Occurrence Handle10.1126/science.1090922
G Aguiari M Banzi S Gessi Y Cai E Zeggio E Manzati et al. (2004) ArticleTitleDeficiency of polycystin-2 reduces Ca2+ channel activity and cell proliferation in ADPKD lymphoblastoid cells FASEB J 18 884–6 Occurrence Handle1:CAS:528:DC%2BD2cXjvVClsb4%3D Occurrence Handle15001556 Occurrence Handle10.1096/fj.03-0687fje
InstitutionalAuthorNameThe International Polycystic Kidney Disease Consortium (1995) ArticleTitlePolycystic kidney disease: the complete structure of the PKD1 gene and its protein Cell 81 289–98 Occurrence Handle10.1016/0092-8674(95)90339-9
PD Wilson (2001) ArticleTitlePolycystin: new aspects of structure, function, and regulation J Am Soc Nephrol 12 834–45 Occurrence Handle1:CAS:528:DC%2BD3MXjtVWgt7g%3D Occurrence Handle11274246
L Geng Y Segal A Pavlova EJ Barros C Lohning W Lu et al. (1997) ArticleTitleDistribution and developmentally regulated expression of murine polycystin Am J Physiol 272 F451–F459 Occurrence Handle1:CAS:528:DyaK2sXjtVSru7c%3D Occurrence Handle9140045
A Boletta F Qian LF Onuchic AK Bhunia B Phakdeekitcharoen K Hanaoka et al. (2000) ArticleTitlePolycystin-1, the gene product of PKD1, induces resistance to apoptosis and spontaneous tubulogenesis in MDCK cells Mol Cell 6 1267–73 Occurrence Handle1:CAS:528:DC%2BD3cXosV2mtL4%3D Occurrence Handle11106764 Occurrence Handle10.1016/S1097-2765(00)00123-4
S Muto A Aiba Y Saito K Nakao K Nakamura K Tomita et al. (2002) ArticleTitlePioglitazone improves the phenotype and molecular defects of a targeted Pkd1 mutant Hum Mol Genet 11 1731–42 Occurrence Handle1:CAS:528:DC%2BD38XlsFCku7o%3D Occurrence Handle12095915 Occurrence Handle10.1093/hmg/11.15.1731
K Kim I Drummond O Ibraghimov-Beskrovnaya K Klinger MA Arnaout (2000) ArticleTitlePolycystin 1 is required for the structural integrity of blood vessels Proc Natl Acad Sci USA 97 1731–6 Occurrence Handle1:CAS:528:DC%2BD3cXhsFCrtrc%3D Occurrence Handle10677526 Occurrence Handle26504 Occurrence Handle10.1073/pnas.040550097
C Boulter S Mulroy S Webb S Fleming K Brindle R Sandford (2001) ArticleTitleCardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene Proc Natl Acad Sci USA 98 12174–9 Occurrence Handle1:CAS:528:DC%2BD3MXns1Cjtr4%3D Occurrence Handle11593033 Occurrence Handle59787 Occurrence Handle10.1073/pnas.211191098
W Lu X Shen A Pavlova M Lakkis CJ Ward et al. (2001) ArticleTitleComparison of Pkd1-targeted mutants reveals that loss of polycystin-1 causes cystogenesis and bone defects Hum Mol Genet 10 2385–96 Occurrence Handle1:CAS:528:DC%2BD3MXos1aqsLY%3D Occurrence Handle11689485 Occurrence Handle10.1093/hmg/10.21.2385
R Guillaume M Trudel (2000) ArticleTitleDistinct and common developmental expression patterns of the murine Pkd2 and Pkd1 genes Mech Dev 93 179–83 Occurrence Handle1:CAS:528:DC%2BD3cXislaru7s%3D Occurrence Handle10781953 Occurrence Handle10.1016/S0925-4773(00)00257-4
L Geng Y Segal B Peissel N Deng Y Pei F Carone et al. (1996) ArticleTitleIdentification and localization of polycystin, the PKD1 gene product J Clin Invest 98 2674–82 Occurrence Handle1:CAS:528:DyaK2sXisFyr Occurrence Handle8981910 Occurrence Handle507729 Occurrence Handle10.1172/JCI119090
R Palsson CP Sharma K Kim M McLaughlin D Brown MA Arnaout (1996) ArticleTitleCharacterization and cell distribution of polycystin, the product of autosomal-dominant polycystic kidney disease gene 1 Mol Med 2 702–11 Occurrence Handle1:CAS:528:DyaK2sXkslyjtQ%3D%3D Occurrence Handle8972485 Occurrence Handle2230129
O Ibraghimov-Beskrovnaya WR Dackowski L Foggensteiner N Coleman S Thiru LR Petry et al. (1997) ArticleTitlePolycystin: in vitro synthesis, in vivo tissue expression, and subcellular localization identifies a large membrane-associated protein Proc Natl Acad Sci USA 94 6397–402 Occurrence Handle1:CAS:528:DyaK2sXjvFCktbY%3D Occurrence Handle9177229 Occurrence Handle21061 Occurrence Handle10.1073/pnas.94.12.6397
GM Xu T Sikaneta BM Sullivan Q Zhang M Andreucci T Stehle et al. (2001) ArticleTitlePolycystin-1 interacts with intermediate filaments J Biol Chem 276 46544–52 Occurrence Handle1:CAS:528:DC%2BD3MXptVymu7c%3D Occurrence Handle11581269 Occurrence Handle10.1074/jbc.M107828200
Y Huan J van Adelsberg (1999) ArticleTitlePolycystin-1, the PKD1 gene product, is in a complex containing E-cadherin and the catenins J Clin Invest 104 1459–68 Occurrence Handle1:CAS:528:DyaK1MXntlyqsrk%3D Occurrence Handle10562308 Occurrence Handle481982 Occurrence Handle10.1172/JCI5111
MS Scheffers P van der Bent F Prins L Spruit MH Breuning SV Litvinov et al. (2000) ArticleTitlePolycystin-1, the product of the polycystic kidney disease 1 gene, co-localizes with desmosomes in MDCK cells Hum Mol Genet 9 2743–50 Occurrence Handle1:CAS:528:DC%2BD3cXosVKktbY%3D Occurrence Handle11063733 Occurrence Handle10.1093/hmg/9.18.2743
A Boletta F Qian LF Onuchic A Bragonzi M Cortese PM Deen et al. (2002) ArticleTitleBiochemical characterization of bona fide polycystin-1 in vitro and in vivo Am J Kidney Dis 38 1421–9 Occurrence Handle10.1053/ajkd.2001.29282 Occurrence Handle1:CAS:528:DC%2BD38XisFCqug%3D%3D
NO Bukanov H Husson WR Dackowski BD Lawrence PA Clow BL Roberts et al. (2002) ArticleTitleFunctional polycystin-1 expression is developmentally regulated during epithelial morphogenesis in vitro: downregulation and loss of membrane localization during cystogenesis Hum Mol Genet 11 923–36 Occurrence Handle1:CAS:528:DC%2BD38XjtlGktro%3D Occurrence Handle10.1093/hmg/11.8.923
S Gonzalez-Perrett K Kim C Ibarra AE Damiano E Zotta M Batelli et al. (2001) ArticleTitlePolycystin-2, the protein mutated in autosomal-dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel Proc Natl Acad Sci USA 98 1182–7 Occurrence Handle1:CAS:528:DC%2BD3MXht1Smt74%3D Occurrence Handle11252306 Occurrence Handle10.1073/pnas.98.3.1182
PM Vassilev L Guo XZ Chen Y Segal JB Peng N Basora et al. (2001) ArticleTitlePolycystin-2 is a novel cation channel implicated in defective intracellular Ca2+ homeostasis in polycystic kidney disease Biochem Biophys Res Commun 282 341–50 Occurrence Handle1:CAS:528:DC%2BD3MXitFeit78%3D Occurrence Handle11264013 Occurrence Handle10.1006/bbrc.2001.4554
P Koulen Y Cai L Geng Y Maeda S Nishimura R Witzgall et al. (2002) ArticleTitlePolycystin-2 is an intracellular calcium release channel Nat Cell Biol 4 191–7 Occurrence Handle1:CAS:528:DC%2BD38XitF2hur4%3D Occurrence Handle11854751 Occurrence Handle10.1038/ncb754
LJ Newby AJ Streets Y Zhao PC Harris CJ Ward ACM Ong (2002) ArticleTitleIdentification, characterization, and localization of a novel kidney polycystin-1–polycystin-2 complex J Biol Chem 277 20763–73 Occurrence Handle1:CAS:528:DC%2BD38XkslWnsrw%3D Occurrence Handle11901144 Occurrence Handle10.1074/jbc.M107788200
K Hanaoka F Qian A Boletta AK Bhunia K Piontek L Tsiokas et al. (2000) ArticleTitleCo-assembly of polycystin-1 and -2 produces unique cation-permeable currents Nature 408 990–4 Occurrence Handle1:CAS:528:DC%2BD3MXhslWqtw%3D%3D Occurrence Handle11140688 Occurrence Handle10.1038/35050128
Y Cai Y Maeda A Cedzich VE Torres GQ Wu T Hayashi et al. (1999) ArticleTitleIdentification and characterization of polycystin-2, the PKD2 gene product J Biol Chem 274 28557–65 Occurrence Handle1:CAS:528:DyaK1MXmsFWgu7s%3D Occurrence Handle10497221 Occurrence Handle10.1074/jbc.274.40.28557
PD Wilson (2004) ArticleTitlePolycystic kidney disease N Engl J Med 350 151–64 Occurrence Handle1:CAS:528:DC%2BD2cXjs1aksQ%3D%3D Occurrence Handle14711914 Occurrence Handle10.1056/NEJMra022161
GJ Pazour JT San Agustin JA Follit JL Rosenbaum GB Witman (2002) ArticleTitlePolycystin-2 localizes to kidney cilia and the ciliary level is elevated in orpk mice with polycystic kidney disease Curr Biol 12 R378–R380 Occurrence Handle1:CAS:528:DC%2BD38XksFOjt70%3D Occurrence Handle12062067 Occurrence Handle10.1016/S0960-9822(02)00877-1
BK Yoder X Hou LM Guay-Woodford (2002) ArticleTitleThe polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia J Am Soc Nephrol 13 2508–16 Occurrence Handle1:CAS:528:DC%2BD38XntVyntr0%3D Occurrence Handle12239239 Occurrence Handle10.1097/01.ASN.0000029587.47950.25
P Delmas (2004) ArticleTitlePolycystins: from mechanosensation to gene regulation Cell 118 145–8 Occurrence Handle1:CAS:528:DC%2BD2cXmtlKnsbc%3D Occurrence Handle15260985 Occurrence Handle10.1016/j.cell.2004.07.007
JJ Grantham JP Calvet (2001) ArticleTitlePolycystic kidney disease: in danger of being X-rated? Proc Natl Acad Sci USA 98 790–2 Occurrence Handle1:CAS:528:DC%2BD3MXht1Sntbc%3D Occurrence Handle11158545 Occurrence Handle33367 Occurrence Handle10.1073/pnas.98.3.790
M Trudel V D'Agati F Costantini (1991) ArticleTitleC-myc as an inducer of polycystic kidney disease in transgenic mice Kidney Int 39 665–71 Occurrence Handle1:STN:280:DyaK3M3mvFKrtg%3D%3D Occurrence Handle1646908 Occurrence Handle10.1038/ki.1991.80
K MacKay LJ Striker CA Pinkert RL Brinster GE Striker (1987) ArticleTitleGlomerulosclerosis and renal cysts in mice transgenic for the early region of SV40 Kidney Int 32 827–37 Occurrence Handle1:STN:280:DyaL1c7hvF2ltg%3D%3D Occurrence Handle2828752 Occurrence Handle10.1038/ki.1987.283
DL Schaffner R Barrios C Massey et al. (1993) ArticleTitleTargeting of the rasT24 oncogene to the proximal convoluted tubules in transgenic mice results in hyperplasia and polycystic kidneys Am J Pathol 142 1051–60 Occurrence Handle1:CAS:528:DyaK3sXltFCrtrs%3D Occurrence Handle8097368 Occurrence Handle1886875
S Horie E Higashihara K Nutahara Y Mikami A Okubo M Kano et al. (1994) ArticleTitleMediation of renal cyst formation by hepatocyte growth factor Lancet 344 789–91 Occurrence Handle1:STN:280:DyaK2czms1Wquw%3D%3D Occurrence Handle7916076 Occurrence Handle10.1016/S0140-6736(94)92344-2
T Nakamura T Nishizawa M Hagiya T Seki M Shimonishi A Sugimura et al. (1989) ArticleTitleMolecular cloning and expression of human hepatocyte growth factor Nature 342 440–3 Occurrence Handle1:CAS:528:DyaK3cXktFyltrc%3D Occurrence Handle2531289 Occurrence Handle10.1038/342440a0
Y Liu (2002) ArticleTitleHepatocyte growth factor and the kidney Curr Opin Nephrol Hypertens 11 23–30 Occurrence Handle11753083 Occurrence Handle10.1097/00041552-200201000-00004
M Rosario W Birchmeier (2003) ArticleTitleHow to make tubes: signaling by the Met receptor tyrosine kinase Trends Cell Biol 13 328–35 Occurrence Handle1:CAS:528:DC%2BD3sXkt1aqsrw%3D Occurrence Handle12791299 Occurrence Handle10.1016/S0962-8924(03)00104-1
H Takayama WJ LaRochelle SG Sabnis T Otsuka G Merlino (1997) ArticleTitleRenal tubular hyperplasia, polycystic disease, and glomerulosclerosis in transgenic mice overexpressing hepatocyte growth factor/scatter factor Lab Invest 77 131–8 Occurrence Handle1:CAS:528:DyaK2sXlvFeis7k%3D Occurrence Handle9274855
P Gual S Giordano S Anguissola PJ Parker PM Comoglio (2001) ArticleTitleGab1 phosphorylation: a novel mechanism for negative regulation of HGF receptor signaling Oncogene 20 156–66 Occurrence Handle1:CAS:528:DC%2BD3MXhtFequ7Y%3D Occurrence Handle11313945 Occurrence Handle10.1038/sj.onc.1204047
S Yamasaki K Nishida Y Yoshida M Itoh M Hibi T Hirano (2003) ArticleTitleGab1 is required for EGF receptor signaling and the transformation by activated ErbB2 Oncogene 22 1546–56 Occurrence Handle1:CAS:528:DC%2BD3sXhvFShurs%3D Occurrence Handle12629518 Occurrence Handle10.1038/sj.onc.1206284
J Du PD Wilson (1995) ArticleTitleAbnormal polarization of EGF receptors and autocrine stimulation of cyst epithelial growth in human ADPKD Am J Physiol 269 C487–C495 Occurrence Handle1:CAS:528:DyaK2MXns1art7k%3D Occurrence Handle7653531 Occurrence Handle10.1152/ajpcell.1995.269.2.C487
WE Sweeney Y Chen K Nakanishi P Frost ED Avner (2000) ArticleTitleTreatment of polycystic kidney disease with a novel tyrosine kinase inhibitor Kidney Int 57 33–40 Occurrence Handle1:CAS:528:DC%2BD3cXivFOltbY%3D Occurrence Handle10620185 Occurrence Handle10.1046/j.1523-1755.2000.00829.x
SK Muthuswamy D Li S Lelievre MJ Bissell JS Brugge (2001) ArticleTitleErbB2, but not ErbB1, reinitiates proliferation and induces luminal repopulation in epithelial acini Nat Cell Biol 3 785–92 Occurrence Handle1:CAS:528:DC%2BD3MXmvF2lsrY%3D Occurrence Handle11533657 Occurrence Handle2952547 Occurrence Handle10.1038/ncb0901-785
R Mangoo-Karim ME Uchic M Grant WA Shumate JP Calvet CH Park et al. (1989) ArticleTitleRenal epithelial fluid secretion and cyst growth: the role of cyclic AMP FASEB J 3 2629–32 Occurrence Handle1:CAS:528:DyaK3cXnsVyhsw%3D%3D Occurrence Handle2480260 Occurrence Handle10.1096/fasebj.3.14.2480260
DP Wallace JJ Grantham LP Sullivan (1996) ArticleTitleChloride and fluid secretion by cultured human polycystic kidney cells Kidney Int 50 1327–36 Occurrence Handle1:CAS:528:DyaK28Xmt1Ojs7k%3D Occurrence Handle8887295 Occurrence Handle10.1038/ki.1996.445
R Mangoo-Karim M Ye DP Wallace JJ Grantham LP Sullivan (1995) ArticleTitleAnion secretion drives fluid secretion by monolayers of cultured human polycystic cells Am J Physiol 269 F381–F388 Occurrence Handle1:CAS:528:DyaK2MXotlClsrk%3D Occurrence Handle7573487
JJ Grantham M Ye VH Gattone LP Sullivan (1999) ArticleTitleIn vitro fluid secretion by epithelium from polycystic kidneys J Clin Invest 95 195–202 Occurrence Handle10.1172/JCI117638
M Ye JJ Grantham (1993) ArticleTitleThe secretion of fluid by renal cysts from patients with autosomal-dominant polycystic kidney disease N Engl J Med 329 310–313 Occurrence Handle1:STN:280:DyaK3szgvFGisw%3D%3D Occurrence Handle8321258 Occurrence Handle10.1056/NEJM199307293290503
T Yamaguchi JC Pelling NT Ramaswamy JW Eppler DP Wallace S Nagao et al. (2000) ArticleTitlecAMP stimulates the in vitro proliferation of renal cyst epithelial cells by activating the extracellular signal-regulated kinase pathway Kidney Int 57 1460–71 Occurrence Handle1:CAS:528:DC%2BD3cXjtVOrt7g%3D Occurrence Handle10760082 Occurrence Handle10.1046/j.1523-1755.2000.00991.x
K Hanaoka WB Guggino (2000) ArticleTitlecAMP regulates cell proliferation and cyst formation in autosomal polycystic kidney disease cells J Am Soc Nephrol 11 1179–87 Occurrence Handle1:CAS:528:DC%2BD3cXltFOjtbo%3D Occurrence Handle10864573
T Yamada Y Terada MK Homma H Nonoguchi S Sasaki Y Tasuhito et al. (1995) ArticleTitleAVP inhibits EGF-stimulated MAP kinase cascade in Madin–Darby canine kidney cells Kidney Int 48 745–52 Occurrence Handle1:CAS:528:DyaK2MXosF2ntrY%3D Occurrence Handle7474660 Occurrence Handle10.1038/ki.1995.346
M Haneda S Araki T Sugimoto M Togawa D Koya R Kikkawa (1996) ArticleTitleDifferential inhibition of mesangial MAP kinase cascade by cyclic nucleotides Kidney Int 50 384–91 Occurrence Handle1:CAS:528:DyaK28XltFyqu70%3D Occurrence Handle8840264 Occurrence Handle10.1038/ki.1996.327
T Yamaguchi DP Wallace BS Magenheimer SJ Hempson JJ Grantham JP Calvet (2004) ArticleTitleCalcium restriction allows cAMP activation of the B-Raf/ERK pathway, switching cells to a cAMP-dependent growth-stimulated phenotype J Biol Chem 279 40419–30 Occurrence Handle1:CAS:528:DC%2BD2cXnslWnsLw%3D Occurrence Handle15263001 Occurrence Handle10.1074/jbc.M405079200
VH Gattone Suffix2nd X Wang PC Harris VE Torres (2003) ArticleTitleInhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist Nat Med 9 1323–6 Occurrence Handle1:CAS:528:DC%2BD3sXns1Cksr4%3D Occurrence Handle14502283 Occurrence Handle10.1038/nm935
CJ Ward et al. (2002) ArticleTitleThe gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein Nat Genet 30 259–69 Occurrence Handle11919560 Occurrence Handle10.1038/ng833
H Olbrich et al. (2003) ArticleTitleMutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosis Nat Genet 34 455–9 Occurrence Handle1:CAS:528:DC%2BD3sXmt1Sku7k%3D Occurrence Handle12872122 Occurrence Handle10.1038/ng1216
D Promeneur T-H Kwon J Frokler MA Knepper S Nielsen (2000) ArticleTitleVasopressin. V2-receptor-dependent regulation of AQP2 expression in Brattleboro rats Am J Physiol Renal Physiol 279 F370–F382 Occurrence Handle1:STN:280:DC%2BD3cvis1ykug%3D%3D Occurrence Handle10919858 Occurrence Handle10.1152/ajprenal.2000.279.2.F370
VE Torres X Wang Q Qian S Somlo PC Harris VH Gattone Suffix2nd (2004) ArticleTitleEffective treatment of an orthologous model of autosomal-dominant polycystic kidney disease Nat Med 10 363–4 Occurrence Handle1:CAS:528:DC%2BD2cXis1ekt7o%3D Occurrence Handle14991049 Occurrence Handle10.1038/nm1004
A Boletta F Qian LF Onuchic AK Bhunia B Phakdeekitcharoen K Hanaoka et al. (2000) ArticleTitlePolycystin-1, the gene product of PKD1, induces resistance to apoptosis and spontaneous tubulogenesis in MDCK cells Mol Cell 6 1267–73 Occurrence Handle1:CAS:528:DC%2BD3cXosV2mtL4%3D Occurrence Handle11106764 Occurrence Handle10.1016/S1097-2765(00)00123-4
AK Bhunia K Piontek A Boletta L Liu F Qian P-N Xu et al. (2002) ArticleTitlePKD1 induces p21waf1 and regulation of the cell cycle via direct activation of the JAK-STAT signaling pathway in a process requiring PKD2 Cell 109 157–68 Occurrence Handle1:CAS:528:DC%2BD38Xjt1ektLk%3D Occurrence Handle12007403 Occurrence Handle10.1016/S0092-8674(02)00716-X
C Boccaccio M Ando L Tamagnone A Bardelli P Michieli C Battistini et al. (1998) ArticleTitleInduction of epithelial tubules by growth factor HGF depends on the STAT pathway Nature 391 285–8 Occurrence Handle1:CAS:528:DyaK1cXnsV2nsQ%3D%3D Occurrence Handle9440692 Occurrence Handle10.1038/34657
SJ Vainio MS Uusitalo (2000) ArticleTitleA road to kidney tubules via the Wnt pathway Pediatr Nephrol 15 151–6 Occurrence Handle1:STN:280:DC%2BD3M7js1Ogsw%3D%3D Occurrence Handle11095034 Occurrence Handle10.1007/s004670000404
E Kim T Arnould LK Sellin T Benzing MJ Fan W Gruning et al. (1999) ArticleTitleThe polycystic kidney disease 1 gene product modulates Wnt signaling J Biol Chem 274 4947–53 Occurrence Handle1:CAS:528:DyaK1MXhsFSlsL4%3D Occurrence Handle9988738 Occurrence Handle10.1074/jbc.274.8.4947
NH Le P van der Bent G Huls M van de Wetering M Loghman-Adham AC Ong et al. (2004) ArticleTitleAberrant polycystin-1 expression results in modification of activator protein-1 activity, whereas Wnt signaling remains unaffected J Biol Chem 279 27472–81 Occurrence Handle1:CAS:528:DC%2BD2cXkvFGntLw%3D Occurrence Handle15087466 Occurrence Handle10.1074/jbc.M312183200
Y Guan MD Breyer (2001) ArticleTitlePeroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease Kidney Int 60 14–30 Occurrence Handle1:CAS:528:DC%2BD3MXltlKntLg%3D Occurrence Handle11422732 Occurrence Handle10.1046/j.1523-1755.2001.00766.x
L Fajas MB Debril J Auwerx (2001) ArticleTitlePeroxisome proliferator-activated receptor-gamma: from adipogenesis to carcinogenesis J Mol Endocrinol 27 1–9 Occurrence Handle1:CAS:528:DC%2BD3MXmtlCrtbw%3D Occurrence Handle11463572 Occurrence Handle10.1677/jme.0.0270001
S Altiok M Xu BM Spiegelman (1997) ArticleTitlePPARγ induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A Genes Dev 11 1987–98 Occurrence Handle1:CAS:528:DyaK2sXlsVSmsbc%3D Occurrence Handle9271121 Occurrence Handle316411 Occurrence Handle10.1101/gad.11.15.1987
E Mueller P Sarraf P Tontonoz et al. (1998) ArticleTitleTerminal differentiation of human breast cancer through PPARγ Mol Cell 1 465–70 Occurrence Handle1:CAS:528:DyaK1cXhtlyhurk%3D Occurrence Handle9660931 Occurrence Handle10.1016/S1097-2765(00)80047-7
P Tontonoz S Singer BM Forman et al. (1997) ArticleTitleTerminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor γ and the retinoid X receptor Proc Natl Acad Sci USA 94 237–41 Occurrence Handle1:CAS:528:DyaK2sXktVGjtA%3D%3D Occurrence Handle8990192 Occurrence Handle19300 Occurrence Handle10.1073/pnas.94.1.237
Y Guan Y Zhang RM Breyer et al. (1999) ArticleTitleExpression of peroxisome proliferator-activated receptor γ (PPARγ) in human transitional bladder cancer and its role in inducing cell death Neoplasia 1 330–9 Occurrence Handle1:CAS:528:DC%2BD3cXksVyhug%3D%3D Occurrence Handle10935488 Occurrence Handle1508103 Occurrence Handle10.1038/sj.neo.7900050
JA Brockman RA Gupta RN DuBois (1998) ArticleTitleActivation of PPARγ leads to inhibition of anchorage-independent growth of human colorectal cancer cells Gastroenterology 115 1049–55 Occurrence Handle1:CAS:528:DyaK1cXntlSgtr0%3D Occurrence Handle9797355 Occurrence Handle10.1016/S0016-5085(98)70072-1
C Boulter S Mulroy S Webb S Fleming K Brindle R Sandford (2001) ArticleTitleCardiovascular, skeletal, and renal defects in mice with a targeted disruption of the Pkd1 gene Proc Natl Acad Sci USA 98 12174–9 Occurrence Handle1:CAS:528:DC%2BD3MXns1Cjtr4%3D Occurrence Handle11593033 Occurrence Handle59787 Occurrence Handle10.1073/pnas.211191098
D Wang J Iversen S Strandgaard (2000) ArticleTitleEndothelium-dependent relaxation of small-resistance vessels is impaired in patients with autosomal dominant polycystic kidney disease J Am Soc Nephrol 11 1371–6 Occurrence Handle1:CAS:528:DC%2BD3cXlvVyhsbY%3D Occurrence Handle10906150
S Moncada A Higgs (1993) ArticleTitleThe arginine–nitric oxide pathway N Engl J Med 329 2002–12 Occurrence Handle1:CAS:528:DyaK2cXhsF2ntrw%3D Occurrence Handle7504210 Occurrence Handle10.1056/NEJM199312303292706
PA Marsden HH Heng SW Scherer et al. (1993) ArticleTitleStructure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene J Biol Chem 268 17478–88 Occurrence Handle1:CAS:528:DyaK3sXmsVansrg%3D Occurrence Handle7688726
A Zanchi DK Moczulski LS Hanna M Wantman JH Warram AS Krolewski (2000) ArticleTitleRisk of advanced diabetic nephropathy in type 1 diabetes is associated with endothelial nitric oxide synthase gene polymorphism Kidney Int 57 405–13 Occurrence Handle1:CAS:528:DC%2BD3cXktFCqs7s%3D Occurrence Handle10652017 Occurrence Handle10.1046/j.1523-1755.2000.00860.x
E Noiri H Satoh J Taguchi et al. (2002) ArticleTitleAssociation of eNOS Glu298Asp polymorphism with end-stage renal disease Hypertension 40 535–40 Occurrence Handle1:CAS:528:DC%2BD38Xntlams7s%3D Occurrence Handle12364359 Occurrence Handle10.1161/01.HYP.0000033974.57407.82
TO Fischmann A Hruza XD Niu et al. (1999) ArticleTitleStructural characterization of nitric oxide synthase isoforms reveals striking active-site conservation Nat Struct Biol 6 233–42 Occurrence Handle1:CAS:528:DyaK1MXhs12rtLo%3D Occurrence Handle10074942 Occurrence Handle10.1038/6675
M Tesauro WC Thompson P Rogliani L Qi PP Chaudhary J Moss (2000) ArticleTitleIntracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298 Proc Natl Acad Sci USA 97 2832–5 Occurrence Handle1:CAS:528:DC%2BD3cXitVahsbo%3D Occurrence Handle10717002 Occurrence Handle16015 Occurrence Handle10.1073/pnas.97.6.2832
A Persu MS Stoenoiu T Messiaen et al. (2002) ArticleTitleModifier effect of ENOS in autosomal-dominant polycystic kidney disease Hum Mol Genet 11 229–41 Occurrence Handle1:CAS:528:DC%2BD38XhvVejsrk%3D Occurrence Handle11823442 Occurrence Handle10.1093/hmg/11.3.229
VE Torres KA Donovan G Scicli KE Holley SN Thibodeau OA Carretero et al. (1992) ArticleTitleSynthesis of renin by tubulocystic epithelium in autosomal-dominant polycystic kidney disease Kidney Int 42 364–73 Occurrence Handle1:STN:280:DyaK3s%2Fit1ehuw%3D%3D Occurrence Handle1405319 Occurrence Handle10.1038/ki.1992.297
SB Harrap DL Davies AM Macnicol AF Dominiczak R Fraser AF Wright et al. (1991) ArticleTitleRenal, cardiovascular and hormonal characteristics of young adults with autosomal-dominant polycystic kidney disease Kidney Int 40 501–8 Occurrence Handle1:STN:280:DyaK387lslClsg%3D%3D Occurrence Handle1838571 Occurrence Handle10.1038/ki.1991.238
AB Chapman A Johnson PA Gabow RW Schrier (1990) ArticleTitleThe renin–angiotensin–aldosterone system and autosomal-dominant polycystic kidney disease N Engl J Med 323 1091–6 Occurrence Handle1:STN:280:DyaK3M%2FhsFaiug%3D%3D Occurrence Handle2215576 Occurrence Handle10.1056/NEJM199010183231602
C Zoja M Abbate D Corna M Capitanio R Donadelli I Bruzzi et al. (1998) ArticleTitlePharmacologic control of angiotensin II ameliorates renal disease while reducing renal TGF-beta in experimental mesangioproliferative glomerulonephritis Am J Kidney Dis 31 453–63 Occurrence Handle1:CAS:528:DyaK1cXitFemtrY%3D Occurrence Handle9506682 Occurrence Handle10.1053/ajkd.1998.v31.pm9506682
M Ruiz-Ortega C Bustos MA Hernandez-Presa O Lorenzo JJ Plaza J Egido (1998) ArticleTitleAngiotensin II participates in mononuclear cell recruitment in experimental immune complex nephritis through nuclear factor-kappa B activation and monocyte chemoattractant protein-1 synthesis J Immunol 161 430–9 Occurrence Handle1:CAS:528:DyaK1cXktVynu7c%3D Occurrence Handle9647253
G Zhou JC Kandala SC Tyagi LC Katwa KT Weber (1996) ArticleTitleEffects of angiotensin II and aldosterone on collagen gene expression and protein turnover in cardiac fibroblasts Mol Cell Biochem 154 171–8 Occurrence Handle1:CAS:528:DyaK28XhtVyrsr8%3D Occurrence Handle8717431 Occurrence Handle10.1007/BF00226785
K Nutahara E Higashihara S Horie K Kamura K Tsuchiya T Mochizuki et al. (2005) ArticleTitleCalcium channel blocker versus angiotensin II receptor blocker in autosomal-dominant polycystic kidney disease Nephron Clin Pract 99 c18–23 Occurrence Handle1:CAS:528:DC%2BD2MXhs1Wksw%3D%3D Occurrence Handle15637459 Occurrence Handle10.1159/000081790
SC Benson HA Pershadsingh CI Ho A Chittiboyina P Desai M Pravenec et al. (2004) ArticleTitleIdentification of telmisartan as a unique angiotensin II receptor antagonist with selective PPAR-gamma-modulating activity Hypertension 43 993–1002 Occurrence Handle1:CAS:528:DC%2BD2cXjt1GmtrY%3D Occurrence Handle15007034 Occurrence Handle10.1161/01.HYP.0000123072.34629.57
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Horie, S. ADPKD: molecular characterization and quest for treatment. Clin Exp Nephrol 9, 282–291 (2005). https://doi.org/10.1007/s10157-005-0367-6
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DOI: https://doi.org/10.1007/s10157-005-0367-6