CKDdb-logoCKDdb - Study ID Exp24726496

PubMed ID24726496
AuthorsWasik AA, Koskelainen S, Hyvonen ME, Musante L, Lehtonen E, Koskenniemi K, Tienari J, Vaheri A, Kerjaschki D, Szalay C, Revesz C, Varmanen P, Nyman TA, Hamar P, Holthofer H, Lehtonen S.
TitleEzrin is down-regulated in diabetic kidney glomeruli and regulates actin reorganization and glucose uptake via GLUT1 in cultured podocytes.
JournalAm J Pathol. 2014 Jun;184(6):1727-39.
AbstractDiabetic nephropathy is a complication of diabetes and a major cause of end-stage renal disease. To characterize the early pathophysiological mechanisms leading to glomerular podocyte injury in diabetic nephropathy, we performed quantitative proteomic profiling of glomeruli isolated from rats with streptozotocin-induced diabetes and controls. Fluorescence-based two-dimensional difference gel electrophoresis, coupled with mass spectrometry, identified 29 differentially expressed spots, including actin-binding protein ezrin and its interaction partner, NHERF2, which were down-regulated in the streptozotocin group. Knockdown of ezrin by siRNA in cultured podocytes increased glucose uptake compared with control siRNA-transfected cells, apparently by increasing translocation of glucose transporter GLUT1 to the plasma membrane. Knockdown of ezrin also induced actin remodeling under basal conditions, but reduced insulin-stimulated actin reorganization. Ezrin-dependent actin remodeling involved cofilin-1 that is essential for the turnover and reorganization of actin filaments. Phosphorylated, inactive cofilin-1 was up-regulated in diabetic glomeruli, suggesting altered actin dynamics. Furthermore, IHC analysis revealed reduced expression of ezrin in the podocytes of patients with diabetes. Our findings suggest that ezrin may play a role in the development of the renal complication in diabetes by regulating transport of glucose and organization of the actin cytoskeleton in podocytes.

Sample characteristics

SpeciesTissue / SourceCompartmentDiseaseDetection methodSample
Rattus norvegicuskidneyglomeruliDiabetesLC-MS/MSDem24726496

Sample description and preparation

Disease (case)diabetic nephropathy
Disease (control)healthy
Disease inductionstreptozotocin, 60 mg/kg
Digestin-gel, trypsin
Separation2-DE

Molecule list

Molecule IDextExternal IDGeneNameSource accRegulation (case/control)Scores
A1374XLMNA_RATLmna, Lmn1, C2.1Prelamin-A/CLMNA_MOUSE quantification method: DIGE
A1374XLMNA_RATLmna, Lmn1, C2.1Prelamin-A/CLMNA_RAT
A1374XLMNA_RATLmna, Lmn1, C2.1Prelamin-A/CLMNA_RAT quantification method: DIGE
A1374XLMNA_RATLmna, Lmn1, C2.1Prelamin-A/CLMNA_RAT
A1374XLMNA_RATLmna, Lmn1, C2.1Prelamin-A/CLMNA_RAT quantification method: DIGE
A1374XLMNA_RATLmna, Lmn1, C2.1Prelamin-A/CLMNA_RAT
A0419XGELS_RATGsnGelsolinGELS_RAT
A0419XGELS_RATGsnGelsolinGELS_RAT
A0909 NHRF2_RATSlc9a3r2, Nherf2Na(+)/H(+) exchange regulatory cofactor NHE-RF2NHRF2_RAT
A1292XUBE2N_RATUbe2nUbiquitin-conjugating enzyme E2 NUBE2N_RAT quantification method: DIGE
A1331XEHD3_RATEhd3, Ehd2EH domain-containing protein 3EHD3_RAT
A1331XEHD3_RATEhd3, Ehd2EH domain-containing protein 3EHD3_RAT
A1971 MAAI_RATGstz1Maleylacetoacetate isomeraseMAAI_MOUSE
A1971 MAAI_RATGstz1Maleylacetoacetate isomeraseMAAI_MOUSE
A2117 PRP19_RATPrpf19, Prp19Pre-mRNA-processing factor 19PRP19_RAT
A371E TAGL2_RATTagln2Transgelin-2TAGL2_RAT
A553CXSSRD_RATSsr4Translocon-associated protein subunit deltaSSRD_RAT quantification method: DIGE
A5632 AADAT_RATAadat, Kat2Kynurenine/alpha-aminoadipate aminotransferaseAADAT_RAT quantification method: DIGE
A5670 ACOC_RATAco1, Ireb1, IrebpCytoplasmic aconitate hydrataseACOC_RAT
A5769 AL9A1_RATAldh9a14-trimethylaminobutyraldehyde dehydrogenaseAL9A1_RAT
A5824 ARK72_RATAkr7a2, Afar2, AiarAflatoxin B1 aldehyde reductase member 2ARK72_RAT
A6466 B0BNJ4Ethe1, Ethe1_predictedEthylmalonic encephalopathy 1ETHE1_MOUSE quantification method: DIGE
A6688 HAOX2_RATHao2, Hao3, Haox2Hydroxyacid oxidase 2HAOX2_RAT
A6688 HAOX2_RATHao2, Hao3, Haox2Hydroxyacid oxidase 2HAOX2_RAT
A0326 EZRI_RATEzr, Vil2EzrinEZRI_RAT
A0442XDPYL2_RATDpysl2Dihydropyrimidinase-related protein 2DPYL2_RAT
A0535XDESM_RATDesDesminDESM_RAT quantification method: DIGE
A0850XVIME_RATVimVimentinVIME_RAT
A3677XQCR2_RATUqcrc2Cytochrome b-c1 complex subunit 2QCR2_RAT
A3694 THIL_RATAcat1Acetyl-CoA acetyltransferaseTHIL_RAT quantification method: DIGE
A496A H2B1_RATHist1h2bg, Hist1h2blHistone H2B type 1H2B1_RAT quantification method: DIGE
A496A H2B1_RATHist1h2bg, Hist1h2blHistone H2B type 1H2B1_RAT quantification method: DIGE
A5661 ACDSB_RATAcadsbShort/branched chain specific acyl-CoA dehydrogenaseACDSB_RAT quantification method: DIGE
A5788XAMACR_RATAmacrAlpha-methylacyl-CoA racemaseAMACR_RAT quantification method: DIGE
A6206XCPT2_RATCpt2, Cpt-2Carnitine O-palmitoyltransferase 2CPT2_RAT quantification method: DIGE
A6321 DHSO_RATSord, Sdh1Sorbitol dehydrogenaseDHSO_RAT
A6644 GPX3_RATGpx3Glutathione peroxidase 3GPX3_RAT quantification method: DIGE
A7132XNDKB_RATNme2Nucleoside diphosphate kinase BNDKB_RAT
A8663XAPOH_RATApohBeta-2-glycoprotein 1APOH_RAT quantification method: DIGE
A9655 RSSA_RATRpsa, Lamr140S ribosomal protein SARSSA_RAT
A1176 APOE_RATApoeApolipoprotein EAPOE_RAT
A1276XCLUS_RATCluClusterinCLUS_RAT quantification method: DIGE
A149C MUP_RATLC11, LOC259246Major urinary proteinMUP_RAT quantification method: DIGE
A3965 TPM1_RATTpm1, Alpha-tm, TpmaTropomyosin alpha-1 chainTPM1_RAT
A6642 GPX1_RATGpx1Glutathione peroxidase 1GPX1_RAT
A1467XFIBA_RATFgaFibrinogen alpha chainFIBA_RAT quantification method: DIGE
A1467XFIBA_RATFgaFibrinogen alpha chainFIBA_RAT quantification method: DIGE
A0647XANXA1_RATAnxa1, Anx1Annexin A1ANXA1_RAT
A0647XANXA1_RATAnxa1, Anx1Annexin A1ANXA1_RAT
A0496 GGT1_RATGgt1, GgtGamma-glutamyltranspeptidase 1GGT1_RAT quantification method: DIGE
A0496 GGT1_RATGgt1, GgtGamma-glutamyltranspeptidase 1GGT1_RAT quantification method: DIGE
A7842 SODC_RATSod1Superoxide dismutase [Cu-Zn]SODC_RAT quantification method: DIGE
A1816 PDIA3_RATPdia3, Erp60, Grp58Protein disulfide-isomerase A3PDIA3_RAT quantification method: DIGE
A7979 THIM_RATAcaa23-ketoacyl-CoA thiolaseTHIM_RAT quantification method: DIGE
A7979 THIM_RATAcaa23-ketoacyl-CoA thiolaseTHIM_RAT quantification method: DIGE
A7979 THIM_RATAcaa23-ketoacyl-CoA thiolaseTHIM_RAT quantification method: DIGE
A1493 FIBB_RATFgbFibrinogen beta chainFIBB_RAT quantification method: DIGE
A5656XACADS_RATAcadsShort-chain specific acyl-CoA dehydrogenaseACADS_RAT quantification method: DIGE
A5656XACADS_RATAcadsShort-chain specific acyl-CoA dehydrogenaseACADS_RAT

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