0000000000535812

AUTHOR

Rosellina M. Mancina

showing 4 related works from this author

Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease.

2022

Background & Aims: Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of macrophage scavenger receptor 1 (MSR1, CD204) remains incompletely understood. Methods: A total of 170 NAFLD liver biopsies were processed for transcriptomic analysis and correlated with clinicopathological features. Msr1(-/-) and wild-type mice were subjected to a 16-week high-fat and high-cholesterol diet. Mice and ex vivo human liver slices were treated with a monoclonal antibody against MSR1. Genetic susceptibility was assessed using genome-wide association study data from 1,483 patients with NAFLD and 430,101 participants of the U…

immunometabolism610 Medicine & healthGastroenterology and HepatologyInbred C57BLDiet High-FatAntibodiesSTEATOHEPATITIS03 medical and health sciencesMice0302 clinical medicineNon-alcoholic Fatty Liver DiseaseMonoclonalGastroenterologiAnimalsHumansObesity610 Medicine & health030304 developmental biologyInflammation0303 health sciencesScience & Technologyimmunometabolism; inflammation; macrophages; NASH; Animals; Antibodies Monoclonal; Diet High-Fat; Genome-Wide Association Study; Humans; Inflammation; Lipids; Liver; Mice; Mice Inbred C57BL; Obesity; Non-alcoholic Fatty Liver DiseaseGastroenterology & HepatologyHepatologyNASHNASH immunometabolism inflammation macrophagesAntibodies MonoclonalLipids3. Good healthmacrophagesDietALPHAMice Inbred C57BLHigh-Fatmacrophages; immunometabolism; NASH; inflammationLiverinflammation3121 General medicine internal medicine and other clinical medicine030211 gastroenterology & hepatologyHuman medicineLife Sciences & BiomedicineGenome-Wide Association StudyJournal of hepatology
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PSD3 downregulation confers protection against fatty liver disease

2022

Fatty liver disease (FLD) is a growing health issue with burdening unmet clinical needs. FLD has a genetic component but, despite the common variants already identified, there is still a missing heritability component. Using a candidate gene approach, we identify a locus (rs71519934) at the Pleckstrin and Sec7 domain-containing 3 (PSD3) gene resulting in a leucine to threonine substitution at position 186 of the protein (L186T) that reduces susceptibility to the entire spectrum of FLD in individuals at risk. PSD3 downregulation by short interfering RNA reduces intracellular lipid content in primary human hepatocytes cultured in two and three dimensions, and in human and rodent hepatoma cell…

GenotypeEndocrinology Diabetes and MetabolismVARIANTSUSCEPTIBILITYPolymorphism Single NucleotideArticleCell LineMiceRibonucleasesPhysiology (medical)Internal MedicineAnimalsGuanine Nucleotide Exchange FactorsHumansRNA-SeqAllelesNon-alcoholic steatohepatitisNONALCOHOLIC STEATOHEPATITISHERITABILITYGene Expression ProfilingfungiNASHGenetic VariationCell BiologyMetabolic syndromeFatty LiverMetabolismGene Expression RegulationLiverEXOME-WIDE ASSOCIATION3121 General medicine internal medicine and other clinical medicineACIDHepatocytesSECRETIONDisease SusceptibilityVLDLBiomarkersTRIGLYCERIDESNon-alcoholic fatty liver disease
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Rare ATG7 genetic variants predispose patients to severe fatty liver disease

2022

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci that contribute to severe NAFLD by examining rare variants.Methods: We performed whole-exome sequencing in in-dividuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n = 301) and examined the enrichment of likely pathogenic rare variants vs. the general population. This was followed by validation at the gene level.Results: In patients with severe NAFLD, we observed an enrichment of the p.P426L variant (rs143545741 C>T; odds ratio [OR] 5.26, 95% CI 2.1-12.6; p = 0.003) of autophagy-rela…

InflammationLiver CirrhosisautophagyHepatologyBiopsyNAFLD NASH autophagy genetics liver fibrosisCarcinomaLiver NeoplasmsNASHHepatocellularAutophagy-Related Protein 7NAFLD; NASH; autophagy; genetics; liver fibrosis; Autophagy-Related Protein 7; Biopsy; Humans; Inflammation; Liver; Liver Cirrhosis; Carcinoma Hepatocellular; Liver Neoplasms; Non-alcoholic Fatty Liver DiseaseLiverNon-alcoholic Fatty Liver DiseaseNAFLDHumansgeneticsgeneticautophagy; genetics; liver fibrosis; NAFLD; NASHliver fibrosis
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Macrophage Scavenger Receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease

2020

AbstractObesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the exact mechanisms remain incompletely understood. Here we demonstrate that macrophage scavenger receptor 1 (MSR1, CD204) expression is associated with the occurrence of hepatic lipid-laden foamy macrophages and correlates with the degree of steatosis and steatohepatitis in a cohort of 170 NAFLD patients. Mice lacking Msr1 are protected against high fat-cholesterol diet (HFD)-induced metabolic disorder, showing fewer hepatic lipid-laden foamy macrophages, less hepatic inflammation, improved dyslipidemia and glucose tolerance, while showing a change in hepatic …

0303 health sciencesmedicine.medical_specialtyLipopolysaccharidebusiness.industryFatty liverInflammationmedicine.disease3. Good healthMSR1Pathogenesis03 medical and health scienceschemistry.chemical_compound0302 clinical medicineEndocrinologychemistryFibrosisInternal medicineMedicine030211 gastroenterology & hepatologySteatohepatitismedicine.symptomSteatosisbusiness030304 developmental biology
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