2015
Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium
McNeer NA, Anandalingam K, Fields RJ, Caputo C, Kopic S, Gupta A, Quijano E, Polikoff L, Kong Y, Bahal R, Geibel JP, Glazer PM, Saltzman WM, Egan ME. Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium. Nature Communications 2015, 6: 6952. PMID: 25914116, PMCID: PMC4480796, DOI: 10.1038/ncomms7952.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineChloridesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDNA-Binding ProteinsGenetic TherapyHigh-Throughput Nucleotide SequencingHumansLactic AcidMice, Inbred C57BLNanoparticlesPeptide Nucleic AcidsPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerPolymersRespiratory MucosaConceptsFacile genome engineeringVivo gene deliveryBiodegradable polymer nanoparticlesTransient gene expressionNanoparticle systemsGene deliveryPolymer nanoparticlesGene correctionGenome engineeringNanoparticlesOff-target effectsPeptide nucleic acidLethal genetic disorderNucleic acidsDonor DNATarget effectsIntranasal deliveryDeliveryCystic fibrosisEngineeringOligonucleotideChloride effluxHuman cellsAirway epitheliumLung tissue
2014
Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1
Vucic E, Alfadda T, MacGregor GG, Dong K, Wang T, Geibel JP. Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1. Pflügers Archiv - European Journal Of Physiology 2014, 467: 1457-1468. PMID: 25127675, DOI: 10.1007/s00424-014-1593-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsGastric AcidGastric MucosaKCNQ1 Potassium ChannelMiceMice, Inbred C57BLPotassium Channels, Inwardly RectifyingStomachXenopusConceptsGastric parietal cellsPotassium channelsParietal cellsΒ-subunitKir1.1 channelsWild-type miceSecretagogue-stimulated gastric acid secretionApical poleGastric glandsLeak pathwayPotential therapeutic targetKir1.1Proton secretionRegulatory characteristicsKv7.1Therapeutic targetATPaseCell numberParietal cell numberCellsNormal gastric acid secretionSecretionInhibitorsAcid secretionMice
2013
Functional vacuolar ATPase (V-ATPase) proton pumps traffic to the enterocyte brush border membrane and require CFTR
Collaco AM, Geibel P, Lee BS, Geibel JP, Ameen NA. Functional vacuolar ATPase (V-ATPase) proton pumps traffic to the enterocyte brush border membrane and require CFTR. American Journal Of Physiology - Cell Physiology 2013, 305: c981-c996. PMID: 23986201, PMCID: PMC4109618, DOI: 10.1152/ajpcell.00067.2013.Peer-Reviewed Original ResearchConceptsV-ATPaseCystic fibrosis transmembrane conductance regulator (CFTR) channelV-ATPase complexV-ATPase functionBrush border membraneProton effluxRat Brunner's glandsIntestinal cellsCAMP/PKACaco-2BBe cellsBorder membraneApical domainCoimmunoprecipitation studiesCFTR distributionVacuolar ATPasesSubapical cytoplasmSpecific subunitsCAMP stimulationProton pumpCAMP treatmentEnterocyte brush border membraneSodium-hydrogen exchangerHydrogen exchangerApical membraneCFTR
2011
Angiotensin II Stimulates H+-ATPase Activity in Intercalated Cells from Isolated Mouse Connecting Tubules and Cortical Collecting Ducts
Wagner CA, Mohebbi N, Uhlig U, Giebisch GH, Breton S, Brown D, Geibel JP. Angiotensin II Stimulates H+-ATPase Activity in Intercalated Cells from Isolated Mouse Connecting Tubules and Cortical Collecting Ducts. Cellular Physiology And Biochemistry 2011, 28: 513-520. PMID: 22116365, PMCID: PMC3709473, DOI: 10.1159/000335112.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAnimalsAnion Transport ProteinsBicarbonatesCell MembraneChloridesColchicineHydrogen-Ion ConcentrationImmunohistochemistryKidney CortexKidney Tubules, CollectingMacrolidesMaleMiceMice, Inbred C57BLReceptors, AngiotensinSaralasinSodiumSulfate TransportersVacuolar Proton-Translocating ATPasesConceptsCNT/CCDAngiotensin IICortical collecting ductsBicarbonate secretionChloride absorptionCollecting ductsType 1 angiotensin II receptorAngiotensin II stimulatesAngiotensin II receptorsAcid-base statusConnecting tubuleATPase activityII receptorsSpecific subtypesNephron segmentsIndependent intracellularAcid extrusionType BSecretionTubulesDuct systemDuctPendrinPresent studyCells
2009
AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion
Sidani S, Kopic S, Socrates T, Kirchhoff P, Föller M, Murek M, Capasso A, Geibel JP. AMP-activated protein kinase: a physiological off switch for murine gastric acid secretion. Pflügers Archiv - European Journal Of Physiology 2009, 459: 39. PMID: 19621238, DOI: 10.1007/s00424-009-0698-3.Peer-Reviewed Original ResearchConceptsProtein kinaseAMPK activationSecretagogue-induced acid secretionCellular ATP levelsPresence of AMPKEnergy-dependent transportersImmunofluorescent localizationParietal cellsGastric glandsCellular ATP consumptionGastric parietal cellsCompound CAMPKProton effluxATP consumptionMetabolic stressRate of intracellularATP levelsKinaseAdenosine monophosphateRegulatorATPLarge abundanceCellsActivation
2006
The KCNE2 Potassium Channel Ancillary Subunit Is Essential for Gastric Acid Secretion*
Roepke TK, Anantharam A, Kirchhoff P, Busque SM, Young JB, Geibel JP, Lerner DJ, Abbott GW. The KCNE2 Potassium Channel Ancillary Subunit Is Essential for Gastric Acid Secretion*. Journal Of Biological Chemistry 2006, 281: 23740-23747. PMID: 16754665, DOI: 10.1074/jbc.m604155200.Peer-Reviewed Original ResearchConceptsAncillary subunitsKCNE gene familyGastric acid secretionPotassium channel alpha subunitFirst genetic evidenceSecretory cellsProton secretionChannel alpha subunitGene familyKCNE familyParietal cell morphologyAcid secretionGenetic evidenceAlpha subunitHuman cardiac arrhythmiasParietal cellsChannel complexSubunitsCell morphologyKCNE2Normal gastrointestinal functionGenesKCNQ1Gene-dose effectCells
2004
Nongenomic stimulation of vacuolar H+-ATPases in intercalated renal tubule cells by aldosterone
Winter C, Schulz N, Giebisch G, Geibel JP, Wagner CA. Nongenomic stimulation of vacuolar H+-ATPases in intercalated renal tubule cells by aldosterone. Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 2636-2641. PMID: 14983061, PMCID: PMC357002, DOI: 10.1073/pnas.0307321101.Peer-Reviewed Original ResearchConceptsAcid-base homeostasisMineralocorticoid receptorStimulatory effectAldosterone-induced stimulationSystemic acid-base homeostasisDistal tubular acidosisRenal tubule cellsAcid-base statusNongenomic modulationNongenomic stimulationRenal collecting ductsAngiotensin IITransepithelial pH gradientTubular acidosisUrine acidificationAldosteroneATPase activityRenal acidificationHydrogen secretionIntracellular Ca2Complete reabsorptionATPase stainingTubule cellsCollecting ductsNongenomic pathways
2003
Localization and Regulation of the ATP6V0A4 (a4) Vacuolar H+-ATPase Subunit Defective in an Inherited Form of Distal Renal Tubular Acidosis
Stehberger PA, Schulz N, Finberg KE, Karet FE, Giebisch G, Lifton RP, Geibel JP, Wagner CA. Localization and Regulation of the ATP6V0A4 (a4) Vacuolar H+-ATPase Subunit Defective in an Inherited Form of Distal Renal Tubular Acidosis. Journal Of The American Society Of Nephrology 2003, 14: 3027-3038. PMID: 14638902, DOI: 10.1097/01.asn.0000099375.74789.ab.Peer-Reviewed Original ResearchConceptsDistal renal tubular acidosisRenal tubular acidosisLoop of HenleProximal tubulesTubular acidosisMouse kidneyA4 expressionDistal tubulesDistal convoluted tubuleProtein expression levelsElectrolyte intakeA4 proteinConvoluted tubulesMouse nephron segmentsNephron segmentsApical stainingWestern blottingAcidosisProtein expressionKidneyATPase activityDistal portionHenleExpression levelsTubulesA rapid enzymatic method for the isolation of defined kidney tubule fragments from mouse
Wagner CA, Lükewille U, Valles P, Breton S, Brown D, Giebisch GH, Geibel JP. A rapid enzymatic method for the isolation of defined kidney tubule fragments from mouse. Pflügers Archiv - European Journal Of Physiology 2003, 446: 623-632. PMID: 12748863, DOI: 10.1007/s00424-003-1082-3.Peer-Reviewed Original ResearchConceptsProximal tubulesTubule fragmentsMouse kidneyKidney tubule fragmentsCollagenase digestion techniqueMouse proximal tubulesUnits/minTrypan blue exclusionKidney functionInner stripeOuter medullaIntercalated cellsIndependent intracellularBlue exclusionTrypan blueTubulesKidneyMicePH-sensitive dyeLight microscopyDuctAnimalsFurther characterizationATPase activityFunctional characteristics
2002
Regulation of the expression of the Cl-/anion exchanger pendrin in mouse kidney by acid-base status
Wagner CA, Finberg KE, Stehberger PA, Lifton RP, Giebisch GH, Aronson PS, Geibel JP. Regulation of the expression of the Cl-/anion exchanger pendrin in mouse kidney by acid-base status. Kidney International 2002, 62: 2109-2117. PMID: 12427135, DOI: 10.1046/j.1523-1755.2002.00671.x.Peer-Reviewed Original ResearchConceptsPendrin-positive cellsAcid-base statusPositive cellsBicarbonate secretionMouse kidneyAcid-base transportKnockout mouse modelProtein expression levelsMetabolic alkalosisDeficient dietExchanger pendrinPendrin expressionMouse modelSensorineural deafnessThyroid glandBicarbonate loadPendred syndromeWestern blottingApical membraneInner earPendrin proteinControl levelsKidneyPendrinProtein levels