CKDdb-logoCKDdb - Study ID Exp19346236

PubMed ID19346236
AuthorsSong X, Di Giovanni V, He N, Wang K, Ingram A, Rosenblum ND, Pei Y.
TitleSystems biology of autosomal dominant polycystic kidney disease (ADPKD): computational identification of gene expression pathways and integrated regulatory networks.
JournalHum Mol Genet. 2009 Jul 1;18(13):2328-43.
AbstractTo elucidate the molecular pathways that modulate renal cyst growth in ADPKD, we performed global gene profiling on cysts of different size (<1 ml, n = 5; 10-20 ml, n = 5; >50 ml, n = 3) and minimally cystic tissue (MCT, n = 5) from five PKD1 human polycystic kidneys using Affymetrix HG-U133 Plus 2.0 arrays. We used gene set enrichment analysis to identify overrepresented signaling pathways and key transcription factors (TFs) between cysts and MCT. We found down-regulation of kidney epithelial restricted genes (e.g. nephron segment-specific markers and cilia-associated cystic genes such as HNF1B, PKHD1, IFT88 and CYS1) in the renal cysts. On the other hand, PKD1 cysts displayed a rich profile of gene sets associated with renal development, mitogen-mediated proliferation, cell cycle progression, epithelial-mesenchymal transition, hypoxia, aging and immune/inflammatory responses. Notably, our data suggest that up-regulation of Wnt/beta-catenin, pleiotropic growth factor/receptor tyrosine kinase (e.g. IGF/IGF1R, FGF/FGFR, EGF/EGFR, VEGF/VEGFR), G-protein-coupled receptor (e.g. PTGER2) signaling was associated with renal cystic growth. By integrating these pathways with a number of dysregulated networks of TFs (e.g. SRF, MYC, E2F1, CREB1, LEF1, TCF7, HNF1B/ HNF1A and HNF4A), our data suggest that epithelial dedifferentiation accompanied by aberrant activation and cross-talk of specific signaling pathways may be required for PKD1 cyst growth and disease progression. Pharmacological modulation of some of these signaling pathways may provide a potential therapeutic strategy for ADPKD.

Sample characteristics

SpeciesTissue / SourceCompartmentDiseaseNDetection method
Homo sapienskidneycystsPolycystic_Kidney_Disease10mRNA microarray

Sample description and preparation

N (case)5
N (control)5
Disease (case)Autosomal dominant polycystic kidney disease
Disease (control)minimally cystic tissue

Sample detection

Array versionAffymetrix HG-U133 Plus 2.0 array

Molecule list

Molecule IDextExternal IDGeneNameRegulation (case/control)Scores
A037C IFT88_HUMANIFT88, TG737, TTC10Intraflagellar transport protein 88 homologp-value: 0.005
A0530XSOCS3_HUMANSOCS3, CIS3, SSI3Suppressor of cytokine signaling 3p-value: 0.005
A0689 AP1M2_HUMANAP1M2Adaptor-related protein complex 1, mu 2 subunitp-value: 0.005
A0705 PGFRA_HUMANPDGFRA, PDGFR2, RHEPDGFRAAlpha platelet-derived growth factor receptor precursorp-value: 0.005
A072F CYS1_HUMANCYS1Cystin-1p-value: 0.005
A0811 IRK1_HUMANKCNJ1, ROMK1ATP-sensitive inward rectifier potassium channel 1p-value: 0.005
A1526 OSTP_HUMANSPP1, BNSP, OPNOsteopontin precursorp-value: 0.005
A1610 LRP2_HUMANLRP2Low-density lipoprotein receptor-related protein 2 precursorp-value: 0.005
A3073XGLI2_HUMANGLI2, THP, Gli2Zinc finger protein GLI2p-value: 0.005
A374C S12A1_HUMANSLC12A1, NKCC2Solute carrier family 12 member 1p-value: 0.005
A376C S12A3_HUMANSLC12A3, TSCSolute carrier family 12 member 3p-value: 0.005
A4505 PKD2_HUMANPKD2, R48321Polycystin 2p-value: 0.005
A4523 SCNNG_HUMANSCNN1GAmiloride-sensitive sodium channel gamma-subunitp-value: 0.005
A475C SC5A2_HUMANSLC5A2, SGLT2Solute carrier family 5 (sodium/glucose cotransporter), member 2p-value: 0.005
A4767XDYH5_HUMANDNAH5, DNAHC5, HL1Ciliary dynein heavy chain 5p-value: 0.005
A547A HNF1A_HUMANHNF1A, TCF1Hepatocyte nuclear factor 1-alphap-value: 0.005
A548A HNF1B_HUMANTCF2, HNF1BHepatocyte nuclear factor 1-betap-value: 0.005
A549A HNF4A_HUMANHNF4A, NR2A1, HNF4Hepatocyte nuclear factor 4-alphap-value: 0.005
A5662 ACE2_HUMANACE2, UNQ868/PRO1885, UNQ868Angiotensin-converting enzyme 2 precursorp-value: 0.005
A5800 AMPN_HUMANCD13, ANPEP, APNAminopeptidase Np-value: 0.005
A6367XDPP4_HUMANDPP4, ADCP2, CD26Dipeptidyl peptidase 4p-value: 0.005
A639A LEG3_HUMANLGALS3, MAC2, GALIGGalectin-3p-value: 0.005
A6483 FAAA_HUMANFAHFumarylacetoacetasep-value: 0.005
A6853XKLK1_HUMANKLK1, KALLIKREINKallikrein 1p-value: 0.005
A6853XKLK1_HUMANKLK1, KALLIKREINKallikrein 1p-value: 0.005
A708B TMM27_HUMANTMEM27, UNQ679/PRO1312, NX17Collectrin precursorp-value: 0.005
A7311 PCKGC_HUMANPCK1, PEPCK1Phosphoenolpyruvate carboxykinase, cytosolic [GTP]p-value: 0.005
A7311 PCKGC_HUMANPCK1, PEPCK1Phosphoenolpyruvate carboxykinase, cytosolic [GTP]p-value: 0.005
A825BXAQP2_HUMANAQP2Aquaporin-CDp-value: 0.005
A8962 PRVA_HUMANPVALBParvalbuminp-value: 0.005
A9139 UROM_HUMANUMODUromodulin precursorp-value: 0.005
A9139 UROM_HUMANUMODUromodulin precursorp-value: 0.005
A925BXCUBN_HUMANCUBN, IFCRCubilinp-value: 0.005
A9447 PKHD1_HUMANPKHD1, FCYT, TIGM1Polycystic kidney and hepatic disease 1 precursorp-value: 0.005
A992B FXYD4_HUMANFXYD4, UNQ526/PRO1069, UNQ526FXYD domain-containing ion transport regulator 4 precursorp-value: 0.005

Compile date 08-10-2018© iMODE-CKD consortium