2024
Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis
Barsotti G, Luciano R, Kumar A, Meliambro K, Kakade V, Tokita J, Naik A, Fu J, Peck E, Pell J, Reghuvaran A, Tanvir E, Patel P, Zhang W, Li F, Moeckel G, Perincheri S, Cantley L, Moledina D, Wilson F, He J, Menon M. Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis. Kidney International Reports 2024, 9: 1354-1368. PMID: 38707807, PMCID: PMC11068976, DOI: 10.1016/j.ekir.2024.02.006.Peer-Reviewed Original ResearchMinimal change diseaseRandomized controlled trialsSafety of metforminDouble-blindPodocyte injuryAdjunctive therapyPlacebo-controlled randomized controlled trialsPhase III studyPhase II trialPrimary glomerular diseaseFocal segmental glomerulosclerosisEffect of metforminPhase IIPlacebo-controlledPreclinical dataNovel urineChange diseaseTissue markersRandomized trialsSegmental glomerulosclerosisGlomerular diseaseMechanistic biomarkersObservational studyFSGSInexpensive agent
2017
Loss of the podocyte glucocorticoid receptor exacerbates proteinuria after injury
Zhou H, Tian X, Tufro A, Moeckel G, Ishibe S, Goodwin J. Loss of the podocyte glucocorticoid receptor exacerbates proteinuria after injury. Scientific Reports 2017, 7: 9833. PMID: 28852159, PMCID: PMC5575043, DOI: 10.1038/s41598-017-10490-z.Peer-Reviewed Original ResearchConceptsKnockout miceGlucocorticoid receptorNephrotic syndromeSimilar renal functionMainstay of therapyReceptor knockout miceTreatment of proteinuriaFoot process effacementMechanism of actionImmunomodulatory therapyRenal functionGlomerular injuryProtein excretionKO miceCommon disorderNephrotoxic serumPodocyte injuryPodocyte-specific deletionMouse modelSlit diaphragm proteinsWild-type podocytesProcess effacementProteinuriaUnstimulated conditionsKnockout animals
2015
Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in Podocytes
Hassan H, Tian X, Inoue K, Chai N, Liu C, Soda K, Moeckel G, Tufro A, Lee AH, Somlo S, Fedeles S, Ishibe S. Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in Podocytes. Journal Of The American Society Of Nephrology 2015, 27: 1055-1065. PMID: 26303067, PMCID: PMC4814187, DOI: 10.1681/asn.2015020191.Peer-Reviewed Original ResearchConceptsX-box binding protein 1Endoplasmic reticulum stress responseEndoplasmic reticulum stressGlomerular filtration barrierPodocyte injuryReticulum stress responseBinding protein 1Reticulum stressProtein 1Filtration barrierFoot process effacementProgressive albuminuriaMouse modelProcess effacementUnfolded protein response pathwayEpithelial cellsNormal glomerular filtration barrierProtein response pathwayEndoplasmic reticulumPodocytesGenetic inactivationXBP1 pathwayInjuryJNK pathwayStress response
2009
Distinct Roles for Basal and Induced COX-2 in Podocyte Injury
Cheng H, Fan X, Guan Y, Moeckel GW, Zent R, Harris RC. Distinct Roles for Basal and Induced COX-2 in Podocyte Injury. Journal Of The American Society Of Nephrology 2009, 20: 1953-1962. PMID: 19643929, PMCID: PMC2736764, DOI: 10.1681/asn.2009010039.Peer-Reviewed Original ResearchMeSH KeywordsAlbuminuriaAnimalsAntibiotics, AntineoplasticApoptosisCell AdhesionCell Line, TransformedCell SurvivalCyclooxygenase 2DinoprostoneDoxorubicinGlomerulonephritisMaleMiceMice, Inbred StrainsMice, TransgenicPodocytesPuromycinReceptors, Prostaglandin EReceptors, ThromboxaneRNA, MessengerThromboxanesConceptsCyclooxygenase-2Thromboxane receptorCOX-2 knockout miceSelective deletionCOX-2 deletionInduced COX-2Receptor subtype 4COX-2 metabolitesFoot process effacementGlomerular injuryPodocyte injuryProstanoid receptorsAttenuated albuminuriaWild-type podocytesSubtype 4Transgenic miceProcess effacementTP antagonistPodocyte survivalInjuryMore prostaglandinsGenetic deletionMicePodocytesGreater expression
2007
Overexpression of Cyclooxygenase-2 Predisposes to Podocyte Injury
Cheng H, Wang S, Jo YI, Hao CM, Zhang M, Fan X, Kennedy C, Breyer MD, Moeckel GW, Harris RC. Overexpression of Cyclooxygenase-2 Predisposes to Podocyte Injury. Journal Of The American Society Of Nephrology 2007, 18: 551-559. PMID: 17202413, DOI: 10.1681/asn.2006090990.Peer-Reviewed Original ResearchConceptsCOX-2 expressionBALB/c miceFoot process effacementTransgenic miceC micePodocyte injuryProcess effacementCOX-2 transgenic miceImmunoreactive COX-2 expressionCOX-2 mRNA expressionNephrin promoterLong-term treatmentCOX-2 overexpressionTransgenic mouse kidneyCyclooxygenase-2 expressionWild-type miceWild-type littermatesCOX-2 mRNARenal injuryRenal ablationAdriamycin nephropathyMore albuminuriaAdriamycin administrationFurther injuryCOX-2