Search results for "Precision-cut tissue slices"

showing 2 items of 2 documents

PI3K inhibition reduces murine and human liver fibrogenesis in precisioncut liver slices

2019

Background: Liver fibrosis results from continuous inflammation and injury. Despite its high prevalence worldwide, no approved antifibrotic therapies exist. Omipalisib is a selective inhibitor of the PI3K/mTOR pathway that controls nutrient metabolism, growth and proliferation. It has shown antifibrotic properties in vitro. While clinical trials for idiopathic pulmonary fibrosis have been initiated, an in-depth preclinical evaluation is lacking. We evaluated omipalisib's effects on fibrogenesis using the ex vivo model of murine and human precision-cut tissue slices (PCTS).Methods: Murine and human liver and jejunum PCTS were incubated with omipalisib up to 10 mu M for 48 h. PI3K pathway act…

0301 basic medicineLiver CirrhosisMalePrecision-cut tissue slicesPROGRESSIONPharmacologyBILIARYBiochemistryPI3KGSK2126458JejunumMicePhosphatidylinositol 3-Kinases0302 clinical medicineAdenosine TriphosphateFibrosisFIBROSIShealth care economics and organizationsPhosphoinositide-3 Kinase InhibitorsSulfonamidesPyridazinesmedicine.anatomical_structureJejunumTARGET030220 oncology & carcinogenesisToxicityQuinolinesPhosphorylationmedicine.symptomATP Binding Cassette Transporter Subfamily BLiver fibrosisEARLY-ONSETInflammation03 medical and health sciencesmedicineAnimalsHumansOmipalisibProtein kinase BPI3K/AKT/mTOR pathwayPharmacologybusiness.industryCUT LIVERmedicine.diseaseMice Inbred C57BLMODEL030104 developmental biologybusinessMATRIXEx vivoBiochemical Pharmacology
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Exploring organ-specific features of fibrogenesis using murine precision-cut tissue slices

2019

Fibrosis is the hallmark of pathologic tissue remodelling in most chronic diseases. Despite advances in our understanding of the mechanisms of fibrosis, it remains uncured. Fibrogenic processes share conserved core cellular and molecular pathways across organs. In this study, we aimed to elucidate shared and organ-specific features of fibrosis using murine precision-cut tissue slices (PCTS) prepared from small intestine, liver and kidneys. PCTS displayed substantial differences in their baseline gene expression profiles: 70% of the extracellular matrix (ECM)-related genes were differentially expressed across the organs. Culture for 48 h induced significant changes in ECM regulation and trig…

Liver CirrhosisEXPRESSION0301 basic medicineINHIBITOR LY2157299 MONOHYDRATEPROTEINPrecision-cut tissue slicesSmad2 ProteinLIVER FIBROSISBiologyKidneyMECHANISMSSMAD2ACTIVATIONPATHWAYExtracellular matrixMiceTGFβ03 medical and health sciences0302 clinical medicineTransforming Growth Factor betaTGF betaFibrosisGene expressionTGF beta signaling pathwaymedicineAnimalsGalunisertibProtein Kinase InhibitorsMolecular BiologyMOLECULAR CHAPERONEGROWTH-FACTOR-BETAKinaseTGF-BETAExtracellular matrixmedicine.diseaseFibrosisPathophysiologyCell biologyMice Inbred C57BL030104 developmental biologyLiver030220 oncology & carcinogenesisQuinolinesPyrazolesMolecular MedicineCollagenHomeostasisSignal TransductionBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
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