2024
Glis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease
Zhang C, Rehman M, Tian X, Pei S, Gu J, Bell T, Dong K, Tham M, Cai Y, Wei Z, Behrens F, Jetten A, Zhao H, Lek M, Somlo S. Glis2 is an early effector of polycystin signaling and a target for therapy in polycystic kidney disease. Nature Communications 2024, 15: 3698. PMID: 38693102, PMCID: PMC11063051, DOI: 10.1038/s41467-024-48025-6.Peer-Reviewed Original ResearchConceptsMouse models of autosomal dominant polycystic kidney diseaseModel of autosomal dominant polycystic kidney diseasePolycystin signalingAutosomal dominant polycystic kidney diseasePolycystin-1Polycystic kidney diseaseTreat autosomal dominant polycystic kidney diseaseGlis2Primary ciliaKidney tubule cellsSignaling pathwayMouse modelDominant polycystic kidney diseasePotential therapeutic targetTranslatomeAntisense oligonucleotidesKidney diseasePolycystinMouse kidneyFunctional effectorsCyst formationTherapeutic targetInactivationFunctional targetPharmacological targetsA synthetic agent ameliorates polycystic kidney disease by promoting apoptosis of cystic cells through increased oxidative stress
Fedeles B, Bhardwaj R, Ishikawa Y, Khumsubdee S, Krappitz M, Gubina N, Volpe I, Andrade D, Westergerling P, Staudner T, Campolo J, Liu S, Dong K, Cai Y, Rehman M, Gallagher A, Ruchirawat S, Croy R, Essigmann J, Fedeles S, Somlo S. A synthetic agent ameliorates polycystic kidney disease by promoting apoptosis of cystic cells through increased oxidative stress. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2317344121. PMID: 38241440, PMCID: PMC10823221, DOI: 10.1073/pnas.2317344121.Peer-Reviewed Original ResearchConceptsCyst cellsAutosomal dominant polycystic kidney diseaseMouse models of autosomal dominant polycystic kidney diseasePolycystic kidney diseaseModel of autosomal dominant polycystic kidney diseaseKidney diseaseDeveloped primersMitochondrial oxidative stressPathophysiology of autosomal dominant polycystic kidney diseaseOxidative stressInduce apoptosisMitochondrial respirationCystic cellsUp-regulating aerobic glycolysisHomozygous inactivationMonogenic causeDominant polycystic kidney diseaseAerobic glycolysisRenal replacement therapyApoptosisEnd-stage kidney diseaseAnti-tumor agentsAdult mouse modelChronic kidney diseaseAlkylate DNA
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
2001
An Amino Acid Triplet in the NH2 Terminus of Rat ROMK1 Determines Interaction with SUR2B*
Dong K, Xu J, Vanoye C, Welch R, MacGregor G, Giebisch G, Hebert S. An Amino Acid Triplet in the NH2 Terminus of Rat ROMK1 Determines Interaction with SUR2B*. Journal Of Biological Chemistry 2001, 276: 44347-44353. PMID: 11567030, DOI: 10.1074/jbc.m108072200.Peer-Reviewed Original Research
2000
Regulation of ROMK1 Channels by Protein-tyrosine Kinase and -tyrosine Phosphatase*
Moral Z, Dong K, Wei Y, Sterling H, Deng H, Ali S, Gu R, Huang X, Hebert S, Giebisch G, Wang W. Regulation of ROMK1 Channels by Protein-tyrosine Kinase and -tyrosine Phosphatase*. Journal Of Biological Chemistry 2000, 276: 7156-7163. PMID: 11114300, PMCID: PMC2822675, DOI: 10.1074/jbc.m008671200.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAnimalsBenzoquinonesBlotting, WesternColchicineConcanavalin AEnzyme InhibitorsLactams, MacrocyclicMicroscopy, FluorescenceMicrotubulesModels, BiologicalMutationOocytesPaclitaxelPatch-Clamp TechniquesPotassiumPotassium ChannelsPotassium Channels, Inwardly RectifyingProtein Tyrosine PhosphatasesProtein-Tyrosine KinasesQuinonesRifabutinRNA, ComplementarySucroseTime FactorsTyrosineXenopusConceptsProtein tyrosine phosphataseProtein tyrosine kinasesHerbimycin AEffect of PAOPhenylarsine oxideROMK1 channelsInhibitor of PTPInhibitors of PTKInhibitors of microtubulesTyrosine phosphataseTreatment of oocytesTyrosine residuesPosition 337Western blot analysisCSrcBlot analysisROMK1OocytesKinaseMicrotubulesTwo-electrode voltage-clamp techniquePhosphataseRegulationRat homolog of sulfonylurea receptor 2B determines glibenclamide sensitivity of ROMK2 in Xenopus laevisoocyte
Tanemoto M, Vanoye C, Dong K, Welch R, Abe T, Hebert S, Xu J. Rat homolog of sulfonylurea receptor 2B determines glibenclamide sensitivity of ROMK2 in Xenopus laevisoocyte. American Journal Of Physiology. Renal Physiology 2000, 278: f659-f666. PMID: 10751228, DOI: 10.1152/ajprenal.2000.278.4.f659.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsATP-Binding Cassette TransportersFemaleGlyburideKidneyMolecular Sequence DataOocytesPotassium ChannelsPotassium Channels, Inwardly RectifyingProtein IsoformsRatsReceptors, DrugSequence Homology, Amino AcidSulfonylurea ReceptorsTranscription, GeneticXenopus laevisConceptsThick ascending limbAscending limbCortical thick ascending limbRT-PCRMedullary thick ascending limbGlibenclamide sensitivityGlibenclamide effectsRat homologIntrarenal distributionSulfonylurea receptor 2BProximal tubulesDistal distributionSulfonylurea receptorRenal ATPSkeletal muscleRat tissuesXenopus laevis oocytesROMK proteinGlibenclamideRat kidney cDNA librarySUR2BTubulesROMKLimbLaevis oocytes