0000000000243955

AUTHOR

Krista Rombouts

0000-0001-9440-0571

showing 3 related works from this author

Genetic association analysis identifies variants associated with disease progression in primary sclerosing cholangitis

2018

ObjectivePrimary sclerosing cholangitis (PSC) is a genetically complex, inflammatory bile duct disease of largely unknown aetiology often leading to liver transplantation or death. Little is known about the genetic contribution to the severity and progression of PSC. The aim of this study is to identify genetic variants associated with PSC disease progression and development of complications.DesignWe collected standardised PSC subphenotypes in a large cohort of 3402 patients with PSC. After quality control, we combined 130 422 single nucleotide polymorphisms of all patients—obtained using the Illumina immunochip—with their disease subphenotypes. Using logistic regression and Cox proportiona…

Male0301 basic medicineOncologyCandidate geneCholangitismedicine.medical_treatmentMedizinTrasplantament hepàticGenome-wide association studyKaplan-Meier EstimateLIVER FIBROSISLiver transplantationBioinformaticsSclerosingOral and gastrointestinalPrimary sclerosing cholangitis; genetics; liver transplantationCohort StudiesACTIVATION0302 clinical medicineMED/12 - GASTROENTEROLOGIAMULTIPLE2.1 Biological and endogenous factorsEPIDEMIOLOGYgeneticsAetiologyCIRRHOSISliver transplantationBilious diseases and biliousnessPrimary sclerosing cholangitisLiver Diseasedigestive oral and skin physiologyGastroenterologySingle NucleotidePrimary sclerosing cholangitiMiddle Aged3. Good healthULCERATIVE-COLITISDisease ProgressionFemale030211 gastroenterology & hepatologyAdultmedicine.medical_specialtyCholangitis SclerosingChronic Liver Disease and CirrhosisClinical SciencesMalalties del tracte biliarSingle-nucleotide polymorphismHEPATIC STELLATE CELLSPolymorphism Single NucleotideInternational PSC Study GroupArticlePrimary sclerosing cholangitisPaediatrics and Reproductive Medicine03 medical and health sciencesRare DiseasesClinical ResearchInternal medicineGeneticsmedicineHumansPolymorphismGENOME-WIDE ASSOCIATIONAlleleDigestive Diseases - (Gallbladder)Survival analysisProportional Hazards ModelsMALIGNANCYThe UK PSC ConsortiumTransplantationGastroenterology & Hepatologybusiness.industryProportional hazards modelmedicine.diseaseRISK LOCILogistic Models030104 developmental biology3121 General medicine internal medicine and other clinical medicinegeneticHepatic transplantationThrombospondinsDigestive DiseasesbusinessGenèticaGut
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Urea cycle dysregulation in non-alcoholic fatty liver disease.

2018

Background & Aims: In non-alcoholic steatohepatitis (NASH), the function of urea cycle enzymes (UCEs) may be affected, resulting in hyperammonemia and the risk of disease progression. We aimed to determine whether the expression and function of UCEs are altered in an animal model of NASH and in patients with non-alcoholic fatty liver disease (NAFLD), and whether this process is reversible. Methods: Rats were first fed a high-fat, high-cholesterol diet for 10 months to induce NASH, before being switched onto a normal chow diet to recover. In humans, we obtained liver biopsies from 20 patients with steatosis and 15 with NASH. Primary rat hepatocytes were isolated and cultured with free fatty …

AdultMale0301 basic medicinemedicine.medical_specialtyCarbamoyl-Phosphate Synthase (Ammonia)Ornithine transcarbamylase03 medical and health scienceschemistry.chemical_compound0302 clinical medicineAmmoniaGlutamate-Ammonia LigaseNon-alcoholic Fatty Liver DiseaseInternal medicineGene expressionmedicineAnimalsHumansUreaRats WistarPromoter Regions GeneticCells CulturedOrnithine CarbamoyltransferaseAgedHepatologyChemistryFatty liverHyperammonemiaDNA MethylationMiddle Agedmedicine.diseaseRats030104 developmental biologyEndocrinologyLiverUrea cycleHepatocytesUreaFemale030211 gastroenterology & hepatologySteatohepatitisSteatosis
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Macrophage MerTK promotes profibrogenic cross-talk with hepatic stellate cells via soluble mediators

2022

Background & aims: Activation of Kupffer cells and recruitment of monocytes are key events in fibrogenesis. These cells release soluble mediators which induce the activation of hepatic stellate cells (HSCs), the main fibrogenic cell type within the liver. Mer tyrosine kinase (MerTK) signaling regulates multiple processes in macrophages and has been implicated in the pathogenesis of non-alcoholic steatohepatitis-related fibrosis. In this study, we explored if MerTK activation in macrophages influences the profibrogenic phenotype of HSCs. Methods: Macrophages were derived from THP-1 cells or differentiated from peripheral blood monocytes towards MerTK+/CD206+/CD163+/CD209- macrophages. Th…

HepatologyCM conditioned medium ECM extracellular matrix Gas-6 Gas-6 growth arrest-specific gene 6 HSC(s) hepatic stellate cells KC(s) Kupffer cell(s) M-CSF macrophage colony-stimulating factor M2c-like macrophages MerTK Myeloid-epithelial-reproductive tyrosine kinase NAFLD non-alcoholic fatty liver disease NASH NASH non-alcoholic steatohepatitis PMA phorbol 12-myristate 13-acetate TGFβ1 transforming growth factor-β1 THP-1 TIMP1 tissue inhibitor of metalloproteinase 1 VEGF-A vascular endothelial growth factor-A liver fibrosis siRNA small-interfering RNAGas-6; liver fibrosis; M2c-like macrophages; NASH; THP-1GastroenterologyInternal MedicineImmunology and AllergyJHEP Reports
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