2023
The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion
Onuchic L, Padovano V, Schena G, Rajendran V, Dong K, Shi X, Pandya R, Rai V, Gresko N, Ahmed O, Lam T, Wang W, Shen H, Somlo S, Caplan M. The C-terminal tail of polycystin-1 suppresses cystic disease in a mitochondrial enzyme-dependent fashion. Nature Communications 2023, 14: 1790. PMID: 36997516, PMCID: PMC10063565, DOI: 10.1038/s41467-023-37449-1.Peer-Reviewed Original ResearchConceptsPolycystin-1Nicotinamide nucleotide transhydrogenaseTerminal tailCystic phenotypeAutosomal dominant polycystic kidney diseaseCyst cell proliferationC-terminal domainAmino acid residuesLethal monogenic disorderC-terminal cleavageNucleotide transhydrogenaseAcid residuesMitochondrial functionTransgenic expressionPKD1 geneRedox stateShort fragmentsCell proliferationMonogenic disordersDominant polycystic kidney diseasePolycystic kidney diseaseGene therapy strategiesProteinPhenotypeFragments
2021
Renal plasticity revealed through reversal of polycystic kidney disease in mice
Dong K, Zhang C, Tian X, Coman D, Hyder F, Ma M, Somlo S. Renal plasticity revealed through reversal of polycystic kidney disease in mice. Nature Genetics 2021, 53: 1649-1663. PMID: 34635846, PMCID: PMC9278957, DOI: 10.1038/s41588-021-00946-4.Peer-Reviewed Original ResearchConceptsPKD genesAutosomal dominant polycystic kidney diseaseCyst cell proliferationGene functionPolycystic kidney diseaseCell shapeGenesKidney diseaseExtracellular matrix depositionCell proliferationKidney tubule cellsNormal lumensDominant polycystic kidney diseaseUnexpected capacityPhenotypic featuresCyst progressionMatrix depositionCellsPlasticityCyst formationCystic tubulesMyofibroblast activationProliferationSquamoid cellsKidney results
2020
Cyclin-Dependent Kinase 1 Activity Is a Driver of Cyst Growth in Polycystic Kidney Disease
Zhang C, Balbo B, Ma M, Zhao J, Tian X, Kluger Y, Somlo S. Cyclin-Dependent Kinase 1 Activity Is a Driver of Cyst Growth in Polycystic Kidney Disease. Journal Of The American Society Of Nephrology 2020, 32: 41-51. PMID: 33046531, PMCID: PMC7894654, DOI: 10.1681/asn.2020040511.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCatalytic DomainCDC2 Protein KinaseCell ProliferationCrosses, GeneticDNA ReplicationExome SequencingFemaleGene Expression ProfilingGene Expression RegulationMaleMiceMice, Inbred C57BLMice, KnockoutMutationPhenotypePolycystic Kidney, Autosomal DominantPyruvate Dehydrogenase Acetyl-Transferring KinaseRNA-SeqTranscription, GeneticTRPP Cation ChannelsConceptsAutosomal dominant polycystic kidney diseaseCyst cell proliferationPolycystic kidney diseaseKidney diseaseADPKD progressionCell proliferationModel of ADPKDCyst growthProgression of ADPKDDominant polycystic kidney diseaseDouble knockout miceCandidate pathwaysKidney functionCyst progressionMouse modelUnbiased transcriptional profilingProgressionCellular mechanismsKinase 1 activityCystic phenotypeSelective targetingKidneyConditional inactivationDouble knockoutProliferation
2016
Double inhibition of cAMP and mTOR signalling may potentiate the reduction of cell growth in ADPKD cells
de Stephanis L, Bonon A, Varani K, Lanza G, Gafà R, Pinton P, Pema M, Somlo S, Boletta A, Aguiari G. Double inhibition of cAMP and mTOR signalling may potentiate the reduction of cell growth in ADPKD cells. Clinical And Experimental Nephrology 2016, 21: 203-211. PMID: 27278932, PMCID: PMC5496448, DOI: 10.1007/s10157-016-1289-1.Peer-Reviewed Original ResearchMeSH KeywordsAdenosineAdenosine A3 Receptor AgonistsAnimalsCell LineCell ProliferationCREB-Binding ProteinCyclic AMPDisease Models, AnimalDrug SynergismDrug Therapy, CombinationExtracellular Signal-Regulated MAP KinasesGenetic Predisposition to DiseaseHumansKidneyMice, Inbred C57BLMice, KnockoutPhenotypePhosphorylationPolycystic Kidney, Autosomal DominantProtein Kinase InhibitorsSignal TransductionSirolimusTime FactorsTOR Serine-Threonine KinasesTRPP Cation ChannelsConceptsCl-IBADPKD patientsCell proliferationADPKD cellsActivation of A3ARCell growthAgonist Cl-IBPolycystin-1MethodsThe inhibitionCombined sequential treatmentRenal functionKidney weightAbnormal cell proliferationERK kinase activityRenal pathologyA3 receptorsInhibition of CREBKidney tissueKinase activityPolycystin-2Marked reductionDirect cell countingKidney cystsMutations of PKD1ERK phosphorylation
2014
Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease (690.2)
Chatsudthipong V, Yuajit C, Muanprasat C, Kittayaruksakul S, Fedeles S, Gallagher A, Somlo S. Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease (690.2). The FASEB Journal 2014, 28 DOI: 10.1096/fasebj.28.1_supplement.690.2.Peer-Reviewed Original ResearchCyst-lining epithelial cellsRenal cyst growthCell proliferationCFTR expressionRenal epithelial cell proliferationMouse modelCyst growthEpithelial cell proliferationPolycystic kidney diseaseEffect of steviolMDCK cyst growthMTOR/S6K pathwayCFTR chloride channelActivation of AMPKCFTR channel activityKidney diseaseOrthologous mouse modelS6K pathwayEpithelial cellsCFTR degradationTransepithelial fluid secretionPKD mouse modelsProtein kinaseS6K expressionPKD genesSteviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease
Yuajit C, Muanprasat C, Gallagher AR, Fedeles SV, Kittayaruksakul S, Homvisasevongsa S, Somlo S, Chatsudthipong V. Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease. Biochemical Pharmacology 2014, 88: 412-421. PMID: 24518257, DOI: 10.1016/j.bcp.2014.01.038.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseasePolycystic kidney diseaseRenal cyst growthCyst-lining epithelial cellsMouse modelKidney diseaseEpithelial cell proliferationEffect of steviolCyst enlargementCyst growthCell proliferationEpithelial cellsBlood urea nitrogenHuman autosomal dominant polycystic kidney diseaseDominant polycystic kidney diseaseOrthologous mouse modelChloride channel expressionRenal epithelial cell proliferationTransepithelial fluid secretionADPKD mouse modelRenal failureKidney functionKidney weightDaily treatmentCreatinine values
2013
Mechanoprotection by Polycystins Against Apoptosis is Mediated Through the Opening of Stretch‐Activated K2P Channels
Duprat F, Peyronnet R, Sharif‐Naeini R, Folgering J, Arhatte M, Jodar M, Boustany C, Gallian C, Tauc M, Duranton C, Rubera I, Lesage F, Pei Y, Peters D, Somlo S, Sachs F, Patel A, Honoré E. Mechanoprotection by Polycystins Against Apoptosis is Mediated Through the Opening of Stretch‐Activated K2P Channels. The FASEB Journal 2013, 27: 912.2-912.2. DOI: 10.1096/fasebj.27.1_supplement.912.2.Peer-Reviewed Original ResearchCell apoptosisTwo-pore KAutosomal dominant polycystic kidney diseaseRenal epithelial cellsTubular cell apoptosisPKD2 geneEpithelial cell proliferationK2P channelsCell proliferationMechanoprotectionPolycystinsApoptosisEpithelial cellsDominant polycystic kidney diseasePKD1Tubular epithelial cell proliferationPolycystic kidney diseaseFunctional relationshipMechanical stressUnresolved questionsCellsFondation de FranceKidney diseaseKidney failureGenes
2012
Polycystin-1 regulates amphiregulin expression through CREB and AP1 signalling: implications in ADPKD cell proliferation
Aguiari G, Bizzarri F, Bonon A, Mangolini A, Magri E, Pedriali M, Querzoli P, Somlo S, Harris PC, Catizone L, del Senno L. Polycystin-1 regulates amphiregulin expression through CREB and AP1 signalling: implications in ADPKD cell proliferation. Journal Of Molecular Medicine 2012, 90: 1267-1282. PMID: 22570239, PMCID: PMC4028691, DOI: 10.1007/s00109-012-0902-3.Peer-Reviewed Original ResearchMeSH KeywordsAmphiregulinAnimalsCell ProliferationCyclic AMPCyclic AMP Response Element-Binding ProteinEGF Family of ProteinsGene SilencingGlycoproteinsHEK293 CellsHumansIntercellular Signaling Peptides and ProteinsMiceMutagenesisMutationOligonucleotide Array Sequence AnalysisPhosphorylationPolycystic Kidney, Autosomal DominantPromoter Regions, GeneticSignal TransductionTranscription Factor AP-1TRPP Cation ChannelsConceptsActivator protein-1Cystic cellsCell proliferationFull-length PC1ADPKD cell proliferationCell growthEpidermal growth factor-like peptidesGrowth factor-like peptidesAutosomal dominant polycystic kidney diseaseRenal cyst developmentAbnormal cell proliferationChromatin immunoprecipitationPolycystin-1Key activatorEGFR activityMicroarray analysisAmphiregulin genesNew potential therapeutic targetsLuciferase assayFactor-like peptidesProtein 1Potential therapeutic targetCell linesAmphiregulin expressionCyst development