CKDdb-logoCKDdb - Study ID Exp17003339b

PubMed ID17003339
AuthorsMakino H, Miyamoto Y, Sawai K, Mori K, Mukoyama M, Nakao K, Yoshimasa Y, Suga S.
TitleAltered gene expression related to glomerulogenesis and podocyte structure in early diabetic nephropathy of db/db mice and its restoration by pioglitazone.
JournalDiabetes. 2006 Oct;55(10):2747-56.
AbstractGlomerular injury plays a pivotal role in the development of diabetic nephropathy. To elucidate molecular mechanisms underlying diabetic glomerulopathy, we compared glomerular gene expression profiles of db/db mice with those of db/m control mice at a normoalbuminuric stage characterized by hyperglycemia and at an early stage of diabetic nephropathy with elevated albuminuria, using cDNA microarray. In db/db mice at the normoalbuminuric stage, hypoxia-inducible factor-1alpha (HIF-1alpha), ephrin B2, glomerular epithelial protein 1, and Pod-1, which play key roles in glomerulogenesis, were already upregulated in parallel with an alteration of genes related to glucose metabolism, lipid metabolism, and oxidative stress. Podocyte structure-related genes, actinin 4alpha and dystroglycan 1 (DG1), were also significantly upregulated at an early stage. The alteration in the expression of these genes was confirmed by quantitative RT-PCR. Through pioglitazone treatment, gene expression of ephrin B2, Pod-1, actinin 4alpha, and DG1, as well as that of oxidative stress and lipid metabolism, was restored concomitant with attenuation of albuminuria. In addition, HIF-1alpha protein expression was partially attenuated by pioglitazone. These results suggest that not only metabolic alteration and oxidative stress, but also the alteration of gene expression related to glomerulogenesis and podocyte structure, may be involved in the pathogenesis of early diabetic glomerulopathy in type 2 diabetes.

Sample characteristics

SpeciesTissue / SourceCompartmentDiseaseNDetection method
Mus musculuskidneyglomeruliDiabetes24cDNA microarray

Sample description and preparation

N (case)12
N (control)12
Disease (case)diabetic nephropathy
Disease (control)healthy, db/m
Disease inductiondb/db, 7w

Sample detection

Array versionAffymetrix Murine Genome U74Av2 GeneChip

Molecule list

Molecule IDextExternal IDGeneNameSource accRegulation (case/control)ValidationScores
A043G CXB2_MOUSEGjb2, Cxn-26Gap junction beta-2 proteinM81445ratio: 0.65 p-value: < 0.05
A1080XCOIA1_MOUSECol18a1Collagen alpha-1(XVIII) chainU03715ratio: 1.91 p-value: < 0.05
A1584XCO4A1_MOUSECol4a1Collagen alpha-1(IV) chainM15832ratio: 2.12 p-value: < 0.05
A3464XPGRC1_MOUSEPgrmc1, PgrmcMembrane-associated progesterone receptor component 1AF042491ratio: 1.69 p-value: < 0.05
A4737 CTGF_MOUSECtgf, Ccn2, Fisp-12Connective tissue growth factorM70642ratio: 1.78 p-value: < 0.05
A5788XAMACR_MOUSEAmacr, Macr1Alpha-methylacyl-CoA racemaseU89906ratio: 0.28 p-value: < 0.05
A5923 BGAL_MOUSEGlb1, Bgl, Glb-1Beta-galactosidaseM57734ratio: 0.52 p-value: < 0.05
A6720 HEXA_MOUSEHexaBeta-hexosaminidase subunit alphaU05837ratio: 1.69 p-value: < 0.05
A6950XMA2A1_MOUSEMan2a1, Mana2Alpha-mannosidase 2X61172ratio: 1.69 p-value: < 0.05
A8378XA2AP_MOUSESerpinf2, PliAlpha-2-antiplasminZ36774ratio: 0.34 p-value: < 0.05
A0647XANXA1_MOUSEAnxa1Annexin A1AV003419ratio: 1.15 p-value: < 0.05
A1563 NPNT_MOUSENpntNephronectinAA592182ratio: 2.58 p-value: < 0.05
A362H MKRN1_MOUSEMkrn1E3 ubiquitin-protein ligase makorin-1AA656621ratio: 0.58 p-value: < 0.05
A7506 PROD2_MOUSEProdh2Probable proline dehydrogenase 2AA675075ratio: 1.96 p-value: < 0.05
A0885 CKS2_MOUSECks2Cyclin-dependent kinases regulatory subunit 2AA681998ratio: 1.96 p-value: < 0.05
A5846XAT11A_MOUSEAtp11aProbable phospholipid-transporting ATPase IHAA690863ratio: 0.22 p-value: < 0.05
A7173 NPL_MOUSENplN-acetylneuraminate lyaseAA710564ratio: 1.96 p-value: < 0.05
AA716963   AA716963AA716963ratio: 0.35 p-value: < 0.05
A349J AK1CL_MOUSEAkr1c21Aldo-keto reductase family 1 member C21AA822174ratio: 0.2 p-value: < 0.05
A6932XLYPA1_MOUSELypla1Acyl-protein thioesterase 1AA840463ratio: 0.61 p-value: < 0.05
A548A HNF1B_MOUSEHnf1b, Hnf-1b, Tcf2Hepatocyte nuclear factor 1-betaAB008174ratio: 0.88 p-value: < 0.05
A6182 CP4AA_MOUSECyp4a10, Cyp4a-10Cytochrome P450 4A10AB018421ratio: 2.34 p-value: < 0.05
A184C NAC1_MOUSESlc8a1Sodium/calcium exchanger 1AF004666ratio: 7.89 p-value: < 0.05
A5679 ACOX1_MOUSEAcox1, Acox, PaoxPeroxisomal acyl-coenzyme A oxidase 1AF006688ratio: 0.56 p-value: < 0.05
A7311 PCKGC_MOUSEPck1, PepckPhosphoenolpyruvate carboxykinase, cytosolic [GTP]AF009605ratio: 1.64 p-value: < 0.05
A015B SMAD6_MOUSESmad6, Madh6, Madh7Mothers against decapentaplegic homolog 6AF010133ratio: 1.65 p-value: < 0.05
A0811 KCNJ1_MOUSEKcnj1ATP-sensitive inward rectifier potassium channel 1AF012834ratio: 2.11 p-value: < 0.05
A273E S100G_MOUSES100g, Calb3, S100dProtein S100-GAF028071ratio: 7.21 p-value: < 0.05
A7364 PGAM2_MOUSEPgam2Phosphoglycerate mutase 2AF029843ratio: 5.47 p-value: < 0.05
A0965 WSB1_MOUSEWsb1WD repeat and SOCS box-containing protein 1AF033186ratio: 6.69 p-value: < 0.05
A1503 PROC_MOUSEProcVitamin K-dependent protein CAF034569ratio: 0.4 p-value: < 0.05
A729I TCF21_MOUSETcf21, Pod1Transcription factor 21AF035717ratio: 0.61method: RT-PCR
A5100 PROM1_MOUSEProm1, Prom, Proml1Prominin-1AF039663ratio: 2.12 p-value: < 0.05
A4327 GRPE2_MOUSEGrpel2, Mt-grpel2GrpE protein homolog 2, mitochondrialAF041060ratio: 0.54 p-value: < 0.05
A7158 NIT1_MOUSENit1Nitrilase homolog 1AF069988ratio: 0.59 p-value: < 0.05
A7767 S27A2_MOUSESlc27a2, Acsvl1, Facvl1Very long-chain acyl-CoA synthetaseAF072757ratio: 0.54 p-value: < 0.05
A322I SAP30_MOUSESap30Histone deacetylase complex subunit SAP30AF075136ratio: 0.36 p-value: < 0.05
A6715 HEPH_MOUSEHephHephaestinAF082567ratio: 2.86 p-value: < 0.05
A0533 S10A1_MOUSES100a1Protein S100-A1AF087687ratio: 1.57 p-value: < 0.05
A6006 CBPN_MOUSECpn1Carboxypeptidase N catalytic chainAI182588ratio: 2.11 p-value: < 0.05
A4784 EMIL1_MOUSEEmilin1EMILIN-1AI315647ratio: 0.29 p-value: < 0.05
A2344XACTN4_MOUSEActn4, FR-17Alpha-actinin-4AI836968ratio: 1.6method: RT-PCR
A6733 HMCS2_MOUSEHmgcs2Hydroxymethylglutaryl-CoA synthase, mitochondrialAI837229ratio: 0.36 p-value: < 0.05
A047J TXNIP_MOUSETxnipThioredoxin-interacting proteinAI839138ratio: 1.3 p-value: < 0.05
A7345 PDK3_MOUSEPdk3[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrialAI842259ratio: 0.49 p-value: < 0.05
A1969 GSTO1_MOUSEGsto1Glutathione S-transferase omega-1AI843119ratio: 1.73 p-value: < 0.05
A1969 GSTO1_MOUSEGsto1Glutathione S-transferase omega-1AI843119ratio: 1.73 p-value: < 0.05
A8998 RCAN1_MOUSERcan1Calcipressin-1AI846152ratio: 2.92 p-value: < 0.05
A3632 LPP3_MOUSEPpap2bLipid phosphate phosphohydrolase 3AI847054ratio: 0.95 p-value: < 0.05
AI848668   AI848668AI848668ratio: 2.06 p-value: < 0.05
A3694 THIL_MOUSEAcat1Acetyl-CoA acetyltransferase, mitochondrialAI849271ratio: 1.82 p-value: < 0.05
A6027 CDK20_MOUSECdk20Cyclin-dependent kinase 20AI849556ratio: 2.01 p-value: < 0.05
AI852641   AI852641AI852641ratio: 2.11 p-value: < 0.05
A102G DEGS2_MOUSEDegs2Sphingolipid delta(4)-desaturase/C4-hydroxylase DES2AI852933ratio: 0.25 p-value: < 0.05
A7345 PDK3_MOUSEPdk3[Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 3, mitochondrialAI853226ratio: 2.12 p-value: < 0.05
AI853977   AI853977AI853977ratio: 0.45 p-value: < 0.05
A6087XCNDP2_MOUSECndp2Cytosolic non-specific dipeptidaseAI854839ratio: 0.11 p-value: < 0.05
A608EXCRTAP_MOUSECrtap, CaspCartilage-associated proteinAJ006469ratio: 0.61 p-value: < 0.05
A6409 ECHP_MOUSEEhhadhPeroxisomal bifunctional enzymeAJ011864ratio: 0.43 p-value: < 0.05
A4744 DAG1_MOUSEDag1DystroglycanAV244370ratio: 1.69method: RT-PCR
A7803 SGK1_MOUSESgk1Serine/threonine-protein kinase Sgk1AW046181ratio: 1.91 p-value: < 0.05
A412E TRI47_MOUSETrim47Tripartite motif-containing protein 47AW048347ratio: 0.59 p-value: < 0.05
A6215 CSAD_MOUSECsadCysteine sulfinic acid decarboxylaseAW120896ratio: 0.56 p-value: < 0.05
A269CXOSBL5_MOUSEOsbpl5Oxysterol-binding protein-related protein 5AW121299ratio: 1.41 p-value: < 0.05
AW122706   AW122706AW122706ratio: 1.82 p-value: < 0.05
A9440 PAR2_MOUSEF2rl1Proteinase-activated receptor 2AW123850ratio: 1.91 p-value: < 0.05
A076F CKLF6_MOUSECmtm6CKLF-like MARVEL transmembrane domain-containing protein 6AW125031ratio: 0.34 p-value: < 0.05
A4687XCNN3_MOUSECnn3Calponin-3AW125626ratio: 1.57 p-value: < 0.05
A349D F1142_MOUSEFam114a2Protein FAM114A2AW125884ratio: 1.65 p-value: < 0.05
A1176 APOE_MOUSEApoeApolipoprotein ED00466ratio: 3.32 p-value: < 0.05
A1198 PTPRD_MOUSEPtprdReceptor-type tyrosine-protein phosphatase deltaD13903ratio: 1.87 p-value: < 0.05
A1276XCLUS_MOUSEClu, Apoj, Msgp-2ClusterinD14077ratio: 4.37 p-value: < 0.05
A857B CALB1_MOUSECalb1CalbindinD26352ratio: 9.97 p-value: < 0.05
A8514 TFPI2_MOUSETfpi2Tissue factor pathway inhibitor 2D50586ratio: 2.17 p-value: < 0.05
A1021 CSRP1_MOUSECsrp1, Crp1, CsrpCysteine and glycine-rich protein 1D88793ratio: 1.91 p-value: < 0.05
FA809 K1B26_MOUSEKlk1b26Kallikrein 1-related peptidase b26J00389ratio: 2.65 p-value: < 0.05
A6962 MAOX_MOUSEMe1, Mod-1, Mod1NADP-dependent malic enzymeJ02652ratio: 0.41 p-value: < 0.05
A6666 GSTA2_MOUSEGsta2Glutathione S-transferase A2J03958ratio: 9.49 p-value: < 0.05
A0419XGELS_MOUSEGsn, GsbGelsolinJ04953ratio: 1.69 p-value: < 0.05
A1501 PROS_MOUSEPros1, ProsVitamin K-dependent protein SL27439ratio: 1.86 p-value: < 0.05
A9139 UROM_MOUSEUmodUromodulinL33406ratio: 0.43 p-value: < 0.05
A6247 DCOR_MOUSEOdc1, OdcOrnithine decarboxylaseM12330ratio: 0.37 p-value: < 0.05
A6853XKLK1_MOUSEKlk1, Klk-6, Klk6Kallikrein-1M13500ratio: 3.86 p-value: < 0.05
A0537XANXA2_MOUSEAnxa2, Anx2, Cal1hAnnexin A2M14044ratio: 1.31 p-value: < 0.05
FA807 K1B22_MOUSEKlk1b22Kallikrein 1-related peptidase b22M1797ratio: 3.96 p-value: < 0.05
A6129 CP2A4_MOUSECyp2a4, Cyp2a-4Cytochrome P450 2A4M19319ratio: 0.32 p-value: < 0.05
A5725 ADH1_MOUSEAdh1, Adh-1Alcohol dehydrogenase 1M22679ratio: 0.23 p-value: < 0.05
A8370 A1AT2_MOUSESerpina1b, Aat2, Dom2Alpha-1-antitrypsin 1-2M25529ratio: 0.8 p-value: < 0.05
A5964XCAH2_MOUSECa2, Car2Carbonic anhydrase 2M25944ratio: 1.92 p-value: < 0.05
A345J ACOD2_MOUSEScd2Acyl-CoA desaturase 2M26270ratio: 2.06 p-value: < 0.05
A5178 TBA1A_MOUSETuba1a, Tuba1Tubulin alpha-1A chainM28729ratio: 1.32 p-value: < 0.05
A5189 TBB2A_MOUSETubb2aTubulin beta-2A chainM28739ratio: 2.79 p-value: < 0.05
A1804XRENI1_MOUSERen1, Ren, Ren-1Renin-1M32352ratio: 2.47 p-value: < 0.05
A5395 MK_MOUSEMdk, MkMidkineM34094ratio: 0.56 p-value: < 0.05
A786I TISB_MOUSEZfp36l1, Brf1, Tis11bZinc finger protein 36, C3H1 type-like 1M58566ratio: 1.35 p-value: < 0.05
A1713 LIPL_MOUSELplLipoprotein lipaseM63335ratio: 0.17 p-value: < 0.05
A4371XPPIC_MOUSEPpic, CypcPeptidyl-prolyl cis-trans isomerase CM74227ratio: 0.55 p-value: < 0.05
A3585 AL1A1_MOUSEAldh1a1, Ahd-2, Ahd2Retinal dehydrogenase 1M74570ratio: 2.11 p-value: < 0.05
A6547XG6PC_MOUSEG6pc, G6ptGlucose-6-phosphataseU00445ratio: 1.25 p-value: < 0.05
A7989 TKT_MOUSETktTransketolaseU05809ratio: 1.91 p-value: < 0.05
A6228 CX6A2_MOUSECox6a2Cytochrome c oxidase subunit 6A2, mitochondrialU08439ratio: 14.9 p-value: < 0.05
A5763XAL3A2_MOUSEAldh3a2, Ahd-3, Ahd3Fatty aldehyde dehydrogenaseU14390ratio: 0.53 p-value: < 0.05
A0518 GHR_MOUSEGhrGrowth hormone receptorU15012ratio: 0.56 p-value: < 0.05
A2620 CDN1C_MOUSECdkn1c, Kip2Cyclin-dependent kinase inhibitor 1CU22399ratio: 1.25 p-value: < 0.05
A1557 EFNB2_MOUSEEfnb2, Elf2, Epl5Ephrin-B2U30244ratio: 1.63method: RT-PCR
A5966 CAH4_MOUSECa4, Car4Carbonic anhydrase 4U37091ratio: 0.54 p-value: < 0.05
A2626 PTPRO_MOUSEPtpro, GLEPP1, Ptpn15Receptor-type tyrosine-protein phosphatase OU37465ratio: 1.16method: RT-PCR
A7843XSODE_MOUSESod3Extracellular superoxide dismutase [Cu-Zn]U38261ratio: 0.7 p-value: < 0.05
A5238 TYB4_MOUSETmsb4x, Ptmb4, Tmsb4Thymosin beta-4U38967ratio: 1.57 p-value: < 0.05
A3267 BCL6_MOUSEBcl6, Bcl-6B-cell lymphoma 6 protein homologU41465ratio: 0.54 p-value: < 0.05
A6046 CGT_MOUSEUgt8, Cgt, Ugt42-hydroxyacylsphingosine 1-beta-galactosyltransferaseU48896ratio: 0.21 p-value: < 0.05
A1630 CD59A_MOUSECd59a, Cd59CD59A glycoproteinU60473ratio: 1.61 p-value: < 0.05
A5406XNDRG1_MOUSENdrg1, Ndr1, NdrlProtein NDRG1U60593ratio: 2.23 p-value: < 0.05
A4358 NPM3_MOUSENpm3Nucleoplasmin-3U64450ratio: 0.46 p-value: < 0.05
A617A IRF6_MOUSEIrf6Interferon regulatory factor 6U73029ratio: 0.88 p-value: < 0.05
A1622 ADML_MOUSEAdmADMU77630ratio: 2.52 p-value: < 0.05
A0942 SOCS2_MOUSESocs2, Cis2, Cish2Suppressor of cytokine signaling 2U88327ratio: 0.49 p-value: < 0.05
A126A SFRP2_MOUSESfrp2, Sarp1, Sdf5Secreted frizzled-related protein 2U88567ratio: 0.9 p-value: < 0.05
A4128XGSH0_MOUSEGclm, GlclrGlutamate--cysteine ligase regulatory subunitU95053ratio: 0.53 p-value: < 0.05
A7502XPRDX4_MOUSEPrdx4Peroxiredoxin-4U96746ratio: 1.91 p-value: < 0.05
FA804 K1KB1_MOUSEKlk1b1, Klk-1, Klk1Kallikrein 1-related peptidase b1V00829ratio: 4.26 p-value: < 0.05
A141C MT1_MOUSEMt1Metallothionein-1V00835ratio: 2.79 p-value: < 0.05
A6157 CP2E1_MOUSECyp2e1, Cyp2e, Cyp2e-1Cytochrome P450 2E1X01026ratio: 0.37 p-value: < 0.05
A1526 OSTP_MOUSESpp1, Eta-1, OpOsteopontinX13986ratio: 2.93 p-value: < 0.05
A242D CTL2A_MOUSECtla2aProtein CTLA-2-alphaX15591ratio: 0.89 p-value: < 0.05
A5077 PGS1_MOUSEBgnBiglycanX53928ratio: 1.45 p-value: < 0.05
A6004XCBPE_MOUSECpeCarboxypeptidase EX61232ratio: 0.17 p-value: < 0.05
A6380 DUS1_MOUSEDusp1, 3ch134, Mkp1Dual specificity protein phosphatase 1X61940ratio: 0.9 p-value: < 0.05
A0536 S10A6_MOUSES100a6, CacyProtein S100-A6X66449ratio: 1.86 p-value: < 0.05
A4777 EGLN_MOUSEEng, EdgEndoglinX77952ratio: 1.34 p-value: < 0.05
A3717XDHI2_MOUSEHsd11b2, Hsd11kCorticosteroid 11-beta-dehydrogenase isozyme 2X90647ratio: 3.86 p-value: < 0.05
A6871 KPYM_MOUSEPkm, Pk3, Pkm2Pyruvate kinase PKMX97047ratio: 2.17 p-value: < 0.05
A1964 GSTT1_MOUSEGstt1Glutathione S-transferase theta-1X98055ratio: 1.52 p-value: < 0.05
A6821 K1KB5_MOUSEKlk1b5, Klk-5, Klk5Kallikrein 1-related peptidase b5Y00500ratio: 3.24 p-value: < 0.05
A534A HIF1A_MOUSEHif1aHypoxia-inducible factor 1-alphaY09085ratio: 1.53method: RT-PCR, Immunohistochemistry
A6185XCP4AE_MOUSECyp4a14Cytochrome P450 4A14Y11638ratio: 15.26 p-value: < 0.05
A3097 KLF9_MOUSEKlf9, Bteb, Bteb-1Krueppel-like factor 9Y14296ratio: 0.62 p-value: < 0.05
A946G IRX3_MOUSEIrx3, Irxb1Iroquois-class homeodomain protein IRX-3Y15001ratio: 0.47 p-value: < 0.05

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