0000000000124402

AUTHOR

Carsten Sticht

showing 6 related works from this author

Evidence for a dysfunction and disease-promoting role of the circadian clock in the diabetic retina.

2021

Diabetic retinopathy is a major complication of chronic hyperglycemia and a leading cause of blindness in developed countries. In the present study the interaction between diabetes and retinal clocks was investigated in mice. It was seen that in the db/db mouse - a widely used animal model of diabetic retinopathy - clock function and circadian regulation of gene expression was disturbed in the retina. Remarkably, elimination of clock function by Bmal1-deficiency mitigates the progression of pathophysiology of the diabetic retina. Thus high-fat diet was seen to induce histopathology and molecular markers associated with diabetic retinopathy in wild type but not in Bmal1-deficient mice. The d…

Blood GlucoseMalemedicine.medical_specialtyCircadian clockCLOCK ProteinsDiseaseChronobiology DisordersPathogenesisCellular and Molecular Neurosciencechemistry.chemical_compoundMiceDiabetes mellitusInternal medicineCircadian ClocksRNA Ribosomal 18SMedicineAnimalsRNA MessengerRetinaDiabetic Retinopathybusiness.industryGlyceraldehyde-3-Phosphate DehydrogenasesRetinalDiabetic retinopathymedicine.diseaseSensory SystemsPathophysiologyCircadian RhythmMice Inbred C57BLOphthalmologyDisease Models Animalmedicine.anatomical_structureEndocrinologychemistryMicroscopy FluorescenceFemalebusinessExperimental eye research
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Transcriptional analysis of rat photoreceptor cells reveals daily regulation of genes important for visual signaling and light damage susceptibility.

2013

Photoreceptor cells face the challenge of adjusting their function and, possibly, their susceptibility to light damage to the marked daily changes in ambient light intensity. To achieve a better understanding of photoreceptor adaptation at the transcriptional level, this study aimed to identify genes which are under daily regulation in photoreceptor cells using microarray analysis and quantitative PCR. Included in the gene set obtained were a number of genes which up until now have not been shown to be expressed in photoreceptor cells, such as Atf3 (activating transcription factor 3) and Pde8a (phosphodiesterase 8A), and others with a known impact on phototransduction and/or photoreceptor s…

MaleTranscription GeneticPhotoperiodActivating transcription factorBiologyBiochemistryPhotoreceptor cellRats Sprague-DawleyCellular and Molecular NeuroscienceGene expressionmedicineTranscriptional regulationAnimalsPhotoreceptor CellsRNA MessengerGeneticsRetinaMicroarray analysis techniquesCell biologyRatsLight intensitymedicine.anatomical_structureGene Expression RegulationVisual Perceptionsense organsPhotic StimulationVisual phototransductionSignal TransductionJournal of neurochemistry
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Cytoplasmic localization of the cell polarity factor scribble supports liver tumor formation and tumor cell invasiveness

2018

The loss of epithelial cell polarity plays an important role in the development and progression of liver cancer. However, the specific molecular mechanisms supporting tumor initiation and progression are poorly understood. In this study, transcriptome data and immunofluorescence stains of tissue samples derived from hepatocellular carcinoma (HCC) patients revealed that overexpression associated with cytoplasmic localization of the baso-lateral cell polarity complex protein Scribble (Scrib) correlated with poor prognosis of HCC patients. In comparison to HCC cells stably expressing wildtype Scrib (ScribWT), mutated Scrib with enforced cytoplasmic enrichment (ScribP305L) induced AKT signaling…

0301 basic medicineSCRIBCytoplasmCarcinoma HepatocellularTumor initiationBiologyMice03 medical and health sciences0302 clinical medicineCell Line TumorCell polarityPhosphoprotein PhosphatasesAnimalsHumansPTENTensinNeoplasm InvasivenessEpithelial–mesenchymal transitionProtein kinase BHepatologyOncogeneTumor Suppressor ProteinsLiver NeoplasmsCell PolarityMembrane ProteinsNuclear ProteinsMolecular biology3. Good healthCell Transformation Neoplastic030104 developmental biologyLiver030220 oncology & carcinogenesisbiology.proteinCancer researchProto-Oncogene Proteins c-aktSignal TransductionHepatology
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Induction of Chromosome Instability by Activation of Yes-Associated Protein and Forkhead Box M1 in Liver Cancer

2016

Background & Aims Many different types of cancer cells have chromosome instability. The hippo pathway leads to phosphorylation of the transcriptional activator yes-associated protein 1 (YAP1, YAP), which regulates proliferation and has been associated with the development of liver cancer. We investigated the effects of hippo signaling via YAP on chromosome stability and hepatocarcinogenesis in humans and mice. Methods We analyzed transcriptome data from 242 patients with hepatocellular carcinoma (HCC) to search for gene signatures associated with chromosomal instability (CIN); we investigated associations with overall survival time and cancer recurrence using Kaplan–Meier curves. We analyze…

0301 basic medicineTime FactorsMuscle ProteinsKaplan-Meier Estimatemedicine.disease_causeChromosome instabilityYAP1Liver NeoplasmsGastroenterologyTEA Domain Transcription FactorsHep G2 CellsPrognosisDNA-Binding ProteinsGene Expression Regulation NeoplasticPhenotypeHippo signalingRNA InterferenceSignal TransductionCarcinoma HepatocellularPorphyrinsAntineoplastic AgentsMice TransgenicBiologyTransfection03 medical and health sciencesChromosomal InstabilitymedicineAnimalsHumansGene silencingGenetic Predisposition to DiseaseAdaptor Proteins Signal TransducingHippo signaling pathwayHepatologyGene Expression ProfilingForkhead Box Protein M1VerteporfinYAP-Signaling ProteinsHCCSPhosphoproteinsThiostreptonMolecular biologyMice Inbred C57BLDisease Models Animal030104 developmental biologyTissue Array AnalysisFOXM1Cancer researchTranscriptomeCarcinogenesisTranscription FactorsGastroenterology
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Renal disease associated with myeloproliferative neoplasms and myelodysplastic syndrome/myeloproliferative neoplasms

2020

Aims Renal changes in patients with myeloproliferative neoplasms (MPNs) or myelodysplastic syndrome (MDS)/MPNs have been addressed by few, respectively no, reports. The aim of this study was to focus on a systematic evaluation of renal biopsies in patients with MPNs or MDS/MPNs. Methods and results The cohort comprised 29 patients (23 men) aged 67 ± 11 years (mean ± standard deviation), diagnosed with chronic myeloid leukaemia (n = 5), polycythaemia vera (n = 9), primary myelofibrosis (n = 5), essential thrombocythaemia (n = 2), or chronic myelomonocytic leukaemia (n = 4), as well as MPNs or MDS/MPNs not otherwise specified (n = 4). Patients manifested with proteinuria (93%), partially in t…

AdultMale0301 basic medicinemedicine.medical_specialtyPolycythaemiaHistologyThrombotic microangiopathy610 MedizinRenal functionMesangial hypercellularityGastroenterologyPathology and Forensic MedicineNephropathyCohort Studies03 medical and health sciencesGlomerulonephritis0302 clinical medicineRisk FactorsNeoplasmshemic and lymphatic diseasesInternal medicine610 Medical sciencesmedicineHumansddc:610MyelofibrosisAgedAged 80 and overMyeloproliferative DisordersProteinuriaThrombotic Microangiopathiesbusiness.industryGlomerulonephritisGeneral MedicineMiddle Agedmedicine.diseaseMyelodysplastic-Myeloproliferative Diseases030104 developmental biologyMyelodysplastic Syndromes030220 oncology & carcinogenesisFemaleKidney Diseasesmedicine.symptombusiness
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The Retinal Clock Drives the Expression ofKcnv2, a Channel Essential for Visual Function and Cone Survival

2012

PURPOSE The gene Kcnv2 codes for the voltage-gated potassium channel subunit Kv8.2, which can coassemble with Kv2.1 subfamily members to constitute functional voltage-gated potassium channels. Mutations in the Kcnv2 gene result in a retinal disorder designated "cone dystrophy with supernormal rod response (CDSRR)," revealing that Kcnv2 is essential for visual processing and cone survival. The aim of this study was to determine whether expression of Kcnv2 and Kv2.1 is under circadian regulation and may thus contribute to the clock-driven adjustment of photoreceptor function. METHODS Expression of the genes was recorded in preparations of the whole retina and microdissected retinal neurons by…

MaleRetinal Disordergenetic structuresCell SurvivalCone dystrophy with supernormal rod responseBlotting WesternBiologyReal-Time Polymerase Chain ReactionRetinaRats Sprague-Dawleychemistry.chemical_compoundShab Potassium ChannelsmedicineTranscriptional regulationAnimalsImmunoprecipitationRNA MessengerGeneVision OcularRetinaRetinalAnatomyAdaptation PhysiologicalPotassium channelCircadian RhythmRatsCell biologymedicine.anatomical_structureReal-time polymerase chain reactionGene Expression RegulationchemistryPotassium Channels Voltage-GatedRetinal Cone Photoreceptor CellsFemalesense organsInvestigative Opthalmology & Visual Science
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