2024
Genetic Analysis of Severe Polycystic Liver Disease in Japan
Mizuno H, Besse W, Sekine A, Long K, Kurihara S, Oba Y, Yamanouchi M, Hasegawa E, Suwabe T, Sawa N, Ubara Y, Somlo S, Hoshino J. Genetic Analysis of Severe Polycystic Liver Disease in Japan. Kidney360 2024, 5: 1106-1115. PMID: 38689396, PMCID: PMC11371350, DOI: 10.34067/kid.0000000000000461.Peer-Reviewed Original ResearchSevere polycystic liver diseaseAutosomal dominant polycystic kidney diseaseDisease genesPolycystic liver diseasePKD2 patientsGenetic analysisWhole-exome sequencingSuspected pathogenic variantsLiver diseaseSpectrum of phenotypesPKD2 variantsExome sequencingAutosomal dominant polycystic kidney disease cohortPathogenic variantsPKD2PKD1Genetic etiologyDominant polycystic kidney diseaseGenesPolycystic kidney diseaseKidney cystsNo significant differenceKidney volumePLD patientsKidney disease
2022
Genetics in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference
Participants K, Köttgen A, Gall E, Halbritter J, Kiryluk K, Mallett A, Parekh R, Rasouly H, Sampson M, Tin A, Antignac C, Ars E, Bergmann C, Bleyer A, Bockenhauer D, Devuyst O, Florez J, Fowler K, Franceschini N, Fukagawa M, Gale D, Gbadegesin R, Goldstein D, Grams M, Greka A, Gross O, Guay-Woodford L, Harris P, Hoefele J, Hung A, Knoers N, Kopp J, Kretzler M, Lanktree M, Lipska-Ziętkiewicz B, Nicholls K, Nozu K, Ojo A, Parsa A, Pattaro C, Pei Y, Pollak M, Rhee E, Sanna-Cherchi S, Savige J, Sayer J, Scolari F, Sedor J, Sim X, Somlo S, Susztak K, Tayo B, Torra R, van Eerde A, Weinstock A, Winkler C, Wuttke M, Zhang H, King J, Cheung M, Jadoul M, Winkelmayer W, Gharavi A. Genetics in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney International 2022, 101: 1126-1141. PMID: 35460632, PMCID: PMC9922534, DOI: 10.1016/j.kint.2022.03.019.Peer-Reviewed Original ResearchConceptsUse of genomicsUse of geneticsGenetic findingsGenome variationNumerous genesMolecular dataGenetic dataComplex kidney diseaseGenetic variantsGeneticsGenesEnvironmental factorsPolygenic scoresMonogenic kidney diseaseGenomicsChronic kidney diseaseImproved diagnosticsInheritanceKidney diseaseData resourcesOpen data resourcesPhenotyping
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
2017
Isolated polycystic liver disease genes define effectors of polycystin-1 function
Besse W, Dong K, Choi J, Punia S, Fedeles SV, Choi M, Gallagher AR, Huang EB, Gulati A, Knight J, Mane S, Tahvanainen E, Tahvanainen P, Sanna-Cherchi S, Lifton RP, Watnick T, Pei YP, Torres VE, Somlo S. Isolated polycystic liver disease genes define effectors of polycystin-1 function. Journal Of Clinical Investigation 2017, 127: 3558-3558. PMID: 28862642, PMCID: PMC5669574, DOI: 10.1172/jci96729.Peer-Reviewed Original ResearchPolycystin-1 functionPolycystin-1Protein biogenesis pathwaysGenome-wide basisPolycystic liver diseaseLoss-of-function mutationsWhole-exome sequencingHeterozygous loss-of-function mutationsBiogenesis pathwayLoss of functionAdditional genesDisease genesGene productsCell line modelsCandidate genesExome sequencingEndoplasmic reticulumCausative genesFunction mutationsGenesAutosomal dominant polycystic kidney diseaseDominant polycystic kidney diseaseSec63Defective maturationKidney cystsIsolated polycystic liver disease genes define effectors of polycystin-1 function
Besse W, Dong K, Choi J, Punia S, Fedeles SV, Choi M, Gallagher AR, Huang EB, Gulati A, Knight J, Mane S, Tahvanainen E, Tahvanainen P, Sanna-Cherchi S, Lifton RP, Watnick T, Pei YP, Torres VE, Somlo S. Isolated polycystic liver disease genes define effectors of polycystin-1 function. Journal Of Clinical Investigation 2017, 127: 1772-1785. PMID: 28375157, PMCID: PMC5409105, DOI: 10.1172/jci90129.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsCalcium-Binding ProteinsCell Line, TransformedCystsEndoplasmic ReticulumFemaleGenome-Wide Association StudyGlucosidasesGlucosyltransferasesHeterozygoteHumansIntracellular Signaling Peptides and ProteinsLiver DiseasesMaleMembrane ProteinsMiceMolecular ChaperonesMutationRNA-Binding ProteinsSEC Translocation ChannelsTRPP Cation ChannelsConceptsPolycystin-1 functionPolycystin-1Protein biogenesis pathwaysGenome-wide basisPolycystic liver diseaseLoss-of-function mutationsWhole-exome sequencingHeterozygous loss-of-function mutationsBiogenesis pathwayLoss of functionAdditional genesDisease genesGene productsCell line modelsCandidate genesExome sequencingEndoplasmic reticulumCausative genesFunction mutationsGenesAutosomal dominant polycystic kidney diseaseDominant polycystic kidney diseaseSec63Defective maturationKidney cysts
2016
mTORC1-mediated inhibition of polycystin-1 expression drives renal cyst formation in tuberous sclerosis complex
Pema M, Drusian L, Chiaravalli M, Castelli M, Yao Q, Ricciardi S, Somlo S, Qian F, Biffo S, Boletta A. mTORC1-mediated inhibition of polycystin-1 expression drives renal cyst formation in tuberous sclerosis complex. Nature Communications 2016, 7: 10786. PMID: 26931735, PMCID: PMC4778067, DOI: 10.1038/ncomms10786.Peer-Reviewed Original ResearchConceptsPolycystin-1Genetic interaction studiesTSC genesPolycystic kidney diseaseTuberous sclerosis complex (TSC) genesKidney-specific inactivationPolycystin-1 expressionRenal cyst formationComplex genesContiguous gene syndromeGenesTsc1 mutantsAutosomal dominant polycystic kidney diseaseOpen new perspectivesDominant polycystic kidney diseaseCyst expansionMTOR inhibitorsNew interplayInteraction studiesTuberous sclerosis complexPKD1 mutationsInactivationCyst formationBiogenesisImportant role
2014
Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney disease
Lee SH, Somlo S. Cyst growth, polycystins, and primary cilia in autosomal dominant polycystic kidney disease. Kidney Research And Clinical Practice 2014, 33: 73-78. PMID: 26877954, PMCID: PMC4714135, DOI: 10.1016/j.krcp.2014.05.002.Peer-Reviewed Original ResearchPrimary ciliaAutosomal dominant polycystic kidney diseaseCarboxy-terminal tailDominant polycystic kidney diseaseExtracellular stimuliPolycystic kidney diseasePolycystin functionChannel proteinsPolycystinsPKD1 geneCystic kidney diseaseCiliaCalcium signalsRenal epitheliumProteinIntact ciliaKidney diseaseGenesCyst growthCurrent understandingReduced levelsPathwayComplete inactivationInactivationRecent data
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
Different effects of Sec61α, Sec62 and Sec63 depletion on transport of polypeptides into the endoplasmic reticulum of mammalian cells
Lang S, Benedix J, Fedeles SV, Schorr S, Schirra C, Schäuble N, Jalal C, Greiner M, Haßdenteufel S, Tatzelt J, Kreutzer B, Edelmann L, Krause E, Rettig J, Somlo S, Zimmermann R, Dudek J. Different effects of Sec61α, Sec62 and Sec63 depletion on transport of polypeptides into the endoplasmic reticulum of mammalian cells. Journal Of Cell Science 2012, 125: 1958-1969. PMID: 22375059, PMCID: PMC4074215, DOI: 10.1242/jcs.096727.Peer-Reviewed Original ResearchConceptsPost-translational transportTail-anchored proteinsSEC61A1 geneEndoplasmic reticulumTransport of polypeptidesCo-translational transportSemi-permeabilized cellsPrecursor proteinSEC62 geneSec61 channelPresecretory proteinsMembrane integrationProtein transportMammalian cellsKnockdown approachHuman cellsGenesHeLa cellsProteinPolypeptideReticulumCellsSec63pSec61αSec63