2015
Human Polycystin-2 Transgene Dose-Dependently Rescues ADPKD Phenotypes in Pkd2 Mutant Mice
Li A, Tian X, Zhang X, Huang S, Ma Y, Wu D, Moeckel G, Somlo S, Wu G. Human Polycystin-2 Transgene Dose-Dependently Rescues ADPKD Phenotypes in Pkd2 Mutant Mice. American Journal Of Pathology 2015, 185: 2843-2860. PMID: 26435415, PMCID: PMC4607765, DOI: 10.1016/j.ajpath.2015.06.014.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseaseMouse modelADPKD phenotypeSevere cystic phenotypeWild-type miceDose-dependent mannerPolycystic kidney diseaseForms of ADPKDKidney diseasePancreatic cystsEffective treatmentFunctional restorationMutant miceTransgene doseMiceCyst formationReduced proliferationEpithelial cellsCystic phenotypeKidneyLiverFurther ameliorationPC2 activityPhenotypeMolecular genetic mechanismsSec63 and Xbp1 regulate IRE1α activity and polycystic disease severity
Fedeles SV, So JS, Shrikhande A, Lee SH, Gallagher AR, Barkauskas CE, Somlo S, Lee AH. Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severity. Journal Of Clinical Investigation 2015, 125: 1955-1967. PMID: 25844898, PMCID: PMC4463201, DOI: 10.1172/jci78863.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineDisease Models, AnimalDNA HelicasesDNA-Binding ProteinsEndoribonucleasesFemaleGlucosidasesIntracellular Signaling Peptides and ProteinsKidneyMaleMiceMice, Inbred C57BLMice, KnockoutMice, TransgenicMolecular ChaperonesPolycystic Kidney, Autosomal DominantPolycystic Kidney, Autosomal RecessiveProtein Serine-Threonine KinasesProtein Structure, TertiaryReceptors, G-Protein-CoupledRecombinant Fusion ProteinsRegulatory Factor X Transcription FactorsRNA SplicingRNA, Small InterferingRNA-Binding ProteinsTranscription FactorsTransfectionTRPP Cation ChannelsUnfolded Protein ResponseX-Box Binding Protein 1ConceptsG protein-coupled receptor proteolysis siteCyst formationPolycystic liver diseaseGPS cleavagePolycystin-1IRE1α-XBP1 branchMurine genetic modelsPolycystic kidney phenotypeLiver diseasePolycystic diseaseCystic diseaseDisease manifestationsMurine modelDisease severityKidney phenotypeXBP1 activationUnfolded protein response pathwayDiseaseXBP1 overexpressionPC1 functionsProtein response pathwayEnforced expressionMiceXBP1Activation of XBP1
2014
Altered trafficking and stability of polycystins underlie polycystic kidney disease
Cai Y, Fedeles SV, Dong K, Anyatonwu G, Onoe T, Mitobe M, Gao JD, Okuhara D, Tian X, Gallagher AR, Tang Z, Xie X, Lalioti MD, Lee AH, Ehrlich BE, Somlo S. Altered trafficking and stability of polycystins underlie polycystic kidney disease. Journal Of Clinical Investigation 2014, 124: 5129-5144. PMID: 25365220, PMCID: PMC4348948, DOI: 10.1172/jci67273.Peer-Reviewed Original ResearchConceptsG-protein-coupled receptor proteolytic sitePolycystic kidney diseaseKidney diseaseGPS cleavageAutosomal dominant polycystic kidney diseaseMissense mutationsDominant polycystic kidney diseasePolycystin-1Polycystin-2Murine modelSevere formPathogenic missense mutationsPKD1 mutationsCOOH-terminal fragmentDiseaseMissense variantsExpression levelsFunctional assaysCell-based systemsAltered trafficking
2013
miR-17∼92 miRNA cluster promotes kidney cyst growth in polycystic kidney disease
Patel V, Williams D, Hajarnis S, Hunter R, Pontoglio M, Somlo S, Igarashi P. miR-17∼92 miRNA cluster promotes kidney cyst growth in polycystic kidney disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 10765-10770. PMID: 23759744, PMCID: PMC3696812, DOI: 10.1073/pnas.1301693110.Peer-Reviewed Original ResearchConceptsMiRNA clusterKidney cyst growthPolycystic kidney diseasePosttranscriptional gene expressionCyst growthOncogenic miRNA clusterShort noncoding RNAsKidney-specific inactivationKidney cyst formationDysregulated miRNA expressionPosttranscriptional repressionNoncoding RNAsHyperproliferative epithelial cellsGene dosageGene expressionHepatocyte nuclear factor-1βGenes PKD1Common genetic causeMiRNA expressionMouse modelFluid-filled cystsMiRNAsKidney diseaseTransgenic overexpressionKidney cysts
2012
Evaluation of urine biomarkers of kidney injury in polycystic kidney disease
Parikh CR, Dahl NK, Chapman AB, Bost JE, Edelstein CL, Comer DM, Zeltner R, Tian X, Grantham JJ, Somlo S. Evaluation of urine biomarkers of kidney injury in polycystic kidney disease. Kidney International 2012, 81: 784-790. PMID: 22258321, PMCID: PMC3319327, DOI: 10.1038/ki.2011.465.Peer-Reviewed Original ResearchMeSH KeywordsAcute-Phase ProteinsAdultAnimalsBiomarkersDisease ProgressionFemaleHumansInterleukin-18KidneyKidney Failure, ChronicLipocalin-2LipocalinsLongitudinal StudiesMaleMiceMice, KnockoutMice, TransgenicOncogene ProteinsPolycystic Kidney, Autosomal DominantProto-Oncogene ProteinsRatsRats, Mutant StrainsRats, Sprague-DawleyReceptors, Interleukin-18TRPP Cation ChannelsConceptsAutosomal dominant polycystic kidney diseaseTotal kidney volumeKidney volumeIL-18Polycystic kidney diseaseKidney diseaseCyst fluidRenal tubular integrityIL-18 levelsRenal Disease equationSerial urine samplesGlomerular filtration rateModification of DietExpression of Lcn2Min/yearPolycystic Kidney Disease (CRISP) studyUrine of patientsDominant polycystic kidney diseaseKidney Disease studyUrinary collecting systemMean percentage increaseSPRD rat modelUrinary NGALUrine NGALKidney injury