2024
Interleukin-7-based identification of liver lymphatic endothelial cells reveals their unique structural features
Yang Y, Jeong J, Su T, Lai S, Zhang P, Garcia-Milian R, Graham M, Liu X, McConnell M, Utsumi T, Pereira J, Iwakiri Y. Interleukin-7-based identification of liver lymphatic endothelial cells reveals their unique structural features. JHEP Reports 2024, 6: 101069. PMID: 38966234, PMCID: PMC11222939, DOI: 10.1016/j.jhepr.2024.101069.Peer-Reviewed Original ResearchCell surface structuresLymphatic endothelial cellsPublished single-cell RNA-sequencingRNA-seq analysisScRNA-seq analysisSingle-cell RNA sequencingLymphatic systemEndothelial cellsInterleukin-7RNA-seqScRNA-seqExpressed genesRNA sequencingTranscriptomic changesLow abundanceI/R liver injuryGenesIsolation protocolLiver cell typesCell typesIsolation methodLiver of miceHuman liver specimensHeterozygous miceMouse liver
2023
The Sympathetic Nervous System Promotes Hepatic Lymphangiogenesis, which Is Protective Against Liver Fibrosis
Tanaka M, Jeong J, Thomas C, Zhang X, Zhang P, Saruwatari J, Kondo R, McConnell M, Utsumi T, Iwakiri Y. The Sympathetic Nervous System Promotes Hepatic Lymphangiogenesis, which Is Protective Against Liver Fibrosis. American Journal Of Pathology 2023, 193: 2182-2202. PMID: 37673329, PMCID: PMC10699132, DOI: 10.1016/j.ajpath.2023.08.004.Peer-Reviewed Original ResearchConceptsPartial portal vein ligationNoncirrhotic portal hypertensionCirrhotic patientsVascular endothelial growth factorLiver fibrosisEndothelial growth factorPortal hypertensionSympathetic denervationSympathetic nervesBDL ratsVascular diseaseIdiopathic noncirrhotic portal hypertensionGrowth factorPortal hypertensive patientsPortal vein ligationSympathetic nervous systemMechanisms of lymphangiogenesisCeliac ganglionectomyHypertensive patientsLymphatic vessel numberLiver biopsyLiver cirrhosisVein ligationPPVL ratsHepatic lymphatic vesselsAn optimized visualization and quantitative protocol for in-depth evaluation of lymphatic vessel architecture in the liver
Jeong J, Tanaka M, Yang Y, Arefyev N, DiRito J, Tietjen G, Zhang X, McConnell M, Utsumi T, Iwakiri Y. An optimized visualization and quantitative protocol for in-depth evaluation of lymphatic vessel architecture in the liver. AJP Gastrointestinal And Liver Physiology 2023, 325: g379-g390. PMID: 37605828, PMCID: PMC10887843, DOI: 10.1152/ajpgi.00139.2023.Peer-Reviewed Original ResearchPortal Hypertension in Alcohol-Associated Hepatitis
McConnell M, Iwakiri Y. Portal Hypertension in Alcohol-Associated Hepatitis. Current Hepatology Reports 2023, 22: 67-73. PMID: 37214274, PMCID: PMC10075503, DOI: 10.1007/s11901-023-00601-y.Peer-Reviewed Original ResearchAlcoholic hepatitisPortal hypertensionMajor public health problemAlcohol‐Associated HepatitisLiver-related morbidityPublic health problemReviewThis review articleIntrahepatic vasoconstrictionHospital admissionPortal inflowPerisinusoidal fibrosisHypertensionHealth problemsLiver vasculatureHepatitisClinical perspectiveMultiple possible mechanismsReview articlePossible mechanismPhlebosclerosisVasoconstrictionMorbidityInflammationAdmissionFibrosisThe evolving role of liver sinusoidal endothelial cells in liver health and disease
McConnell M, Kostallari E, Ibrahim S, Iwakiri Y. The evolving role of liver sinusoidal endothelial cells in liver health and disease. Hepatology 2023, 78: 649-669. PMID: 36626620, PMCID: PMC10315420, DOI: 10.1097/hep.0000000000000207.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsLiver diseaseAlcohol-associated liver diseaseEndothelial cellsLiver transplant rejectionIschemia-reperfusion injuryLiver sinusoidal endothelial cellsSinusoidal endothelial cellsPortal hypertensionLiver inflammationMicrovascular thrombosisViral hepatitisReperfusion injuryTransplant rejectionLiver healthLiver pathologyLiver homeostasisLiver regenerationQuiescent phenotypePathological processesUnique populationDiseaseLSECLiver biologyGene expression profilesInflammation
2022
Plasma Proteomic Profiling Illustrates Endothelial and Complement Signature in Patients with Alcohol-Associated Cirrhosis
Allen C, Butt A, Zhao X, Li F, Bahel P, Chang C, Chun H, Gu S, Hwa J, Jakab S, Chen B, Garcia-Tsao G, Rinder H, To U, McConnell M, Lee A, Pine A. Plasma Proteomic Profiling Illustrates Endothelial and Complement Signature in Patients with Alcohol-Associated Cirrhosis. Blood 2022, 140: 8382-8383. DOI: 10.1182/blood-2022-162633.Peer-Reviewed Original Research
2021
Pathological characteristics of liver sinusoidal thrombosis in COVID‐19 patients: A series of 43 cases
Kondo R, Kawaguchi N, McConnell MJ, Sonzogni A, Licini L, Valle C, Bonaffini PA, Sironi S, Alessio MG, Previtali G, Seghezzi M, Zhang X, Sun Z, Utsumi T, Strazzabosco M, Iwakiri Y. Pathological characteristics of liver sinusoidal thrombosis in COVID‐19 patients: A series of 43 cases. Hepatology Research 2021, 51: 1000-1006. PMID: 34260803, PMCID: PMC8444906, DOI: 10.1111/hepr.13696.Peer-Reviewed Original ResearchCOVID-19 patientsVon Willebrand factorLiver injuryPatient's liverPapa Giovanni XXIII HospitalHigher serum ALTLiver sinusoidal endothelial cellsLiver biopsy samplesSinusoidal endothelial cellsSinusoidal thrombosisSerum ALTAST levelsPathological characteristicsHigher fibrinogenPlatelet microthrombiBiopsy samplesMultiple organsPatientsDisease severityCoronavirus diseaseLiverEndothelial cellsInjurySecondary damageWillebrand factorLiver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy
McConnell MJ, Kawaguchi N, Kondo R, Sonzogni A, Licini L, Valle C, Bonaffini PA, Sironi S, Alessio MG, Previtali G, Seghezzi M, Zhang X, Lee A, Pine AB, Chun HJ, Zhang X, Fernandez-Hernando C, Qing H, Wang A, Price C, Sun Z, Utsumi T, Hwa J, Strazzabosco M, Iwakiri Y. Liver injury in COVID-19 and IL-6 trans-signaling-induced endotheliopathy. Journal Of Hepatology 2021, 75: 647-658. PMID: 33991637, PMCID: PMC8285256, DOI: 10.1016/j.jhep.2021.04.050.Peer-Reviewed Original ResearchConceptsLiver sinusoidal endothelial cellsLiver injuryInterleukin-6Sinusoidal endothelial cellsAlanine aminotransferaseLiver histologyD-dimerCOVID-19Primary human liver sinusoidal endothelial cellsSARS-CoV-2 infectionHuman liver sinusoidal endothelial cellsEndothelial cellsSoluble glycoprotein 130IL-6 levelsSmall-interfering RNA knockdownJAK inhibitor ruxolitinibFactor VIII activityProinflammatory factorsInflammatory signalsLarge cohortInhibitor ruxolitinibVWF antigenEndotheliopathyPatientsInjuryAlcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcohol-related liver disease
Yang Y, Sangwung P, Kondo R, Jung Y, McConnell MJ, Jeong J, Utsumi T, Sessa WC, Iwakiri Y. Alcohol-induced Hsp90 acetylation is a novel driver of liver sinusoidal endothelial dysfunction and alcohol-related liver disease. Journal Of Hepatology 2021, 75: 377-386. PMID: 33675874, PMCID: PMC8292196, DOI: 10.1016/j.jhep.2021.02.028.Peer-Reviewed Original ResearchConceptsEndothelial nitric oxide synthaseAlcohol-induced liver injuryLiver sinusoidal endothelial cellsAlcohol-related liver diseaseLiver injuryLSEC dysfunctionHsp90 acetylationNO productionHistone deacetylase 6Liver diseaseTherapeutic strategiesHeat shock protein 90 (Hsp90) acetylationLiver sinusoidal endothelial dysfunctionSinusoidal endothelial cell dysfunctionMouse liver sinusoidal endothelial cellsEndothelial cell dysfunctionNitric oxide synthaseEthanol-fed miceSinusoidal endothelial dysfunctionPotential therapeutic approachPotential therapeutic strategyNitric oxide productionNew therapeutic strategiesSinusoidal endothelial cellsAcetylation of Hsp90
2020
Single-Cell Transcriptomics Reveals Zone-Specific Alterations of Liver Sinusoidal Endothelial Cells in Cirrhosis
Su T, Yang Y, Lai S, Jeong J, Jung Y, McConnell M, Utsumi T, Iwakiri Y. Single-Cell Transcriptomics Reveals Zone-Specific Alterations of Liver Sinusoidal Endothelial Cells in Cirrhosis. Cellular And Molecular Gastroenterology And Hepatology 2020, 11: 1139-1161. PMID: 33340713, PMCID: PMC7903131, DOI: 10.1016/j.jcmgh.2020.12.007.Peer-Reviewed Original ResearchConceptsLiver sinusoidal endothelial cellsCirrhotic miceSinusoidal endothelial cellsLiver cirrhosisEndothelial cellsIntrahepatic vascular resistanceCarbon tetrachloride inhalationNovel therapeutic strategiesNitric oxide productionCirrhotic mouse liverEC populationsVascular resistanceClinical complicationsLiver fibrosisTherapeutic strategiesCirrhosisOxide productionEndocytic receptorMiceAbstractTextZone 3Extracellular matrix genesVascular ECsLymphatic ECsMouse liverEnhanced Meningeal Lymphatic Drainage Ameliorates Neuroinflammation and Hepatic Encephalopathy in Cirrhotic Rats
Hsu SJ, Zhang C, Jeong J, Lee SI, McConnell M, Utsumi T, Iwakiri Y. Enhanced Meningeal Lymphatic Drainage Ameliorates Neuroinflammation and Hepatic Encephalopathy in Cirrhotic Rats. Gastroenterology 2020, 160: 1315-1329.e13. PMID: 33227282, PMCID: PMC7956141, DOI: 10.1053/j.gastro.2020.11.036.Peer-Reviewed Original ResearchConceptsMeningeal lymphatic drainageLymphatic drainageMicroglia activationMotor functionBile duct ligation modelTumor necrosis factor αSerious neurologic complicationsMeningeal lymphatic systemNecrosis factor αDuct ligation modelNew therapeutic strategiesBrain inflammationNeurologic complicationsHepatic encephalopathyLiver cirrhosisLymph nodesRotarod testMotor dysfunctionCirrhotic ratsInterleukin-1βLigation modelInterferon γProinflammatory genesCisterna magnaTherapeutic strategies
2018
Integrated analysis of microRNA and mRNA expression profiles in splenomegaly induced by non-cirrhotic portal hypertension in rats
Saruwatari J, Dong C, Utsumi T, Tanaka M, McConnell M, Iwakiri Y. Integrated analysis of microRNA and mRNA expression profiles in splenomegaly induced by non-cirrhotic portal hypertension in rats. Scientific Reports 2018, 8: 17983. PMID: 30573742, PMCID: PMC6301948, DOI: 10.1038/s41598-018-36297-0.Peer-Reviewed Original ResearchConceptsCell proliferationWhole-genome microarray analysisInterferon-mediated antiviral activitySuppression of genesMicroRNA-mRNA networkSignificant differential expressionPotential biological functionsMRNA expression profilesTarget mRNAsBiological functionsExpression profilesMicroarray analysisDifferential expressionInnate immune responseMicroRNAsCellular mechanismsHematopoietic systemIntegrated analysisGenesNew insightsComprehensive profileMRNAProliferationTissue fibrosisImportant roleHepatitis C Vaccine Development in the Era of Direct‐Acting Antivirals
McConnell M, Lim JK. Hepatitis C Vaccine Development in the Era of Direct‐Acting Antivirals. Clinical Liver Disease 2018, 12: 118-121. PMID: 30988925, PMCID: PMC6385923, DOI: 10.1002/cld.753.Peer-Reviewed Original ResearchExploring opportunities to prevent cirrhosis admissions in the emergency department: A multicenter multidisciplinary survey
Siddique SM, Lane‐Fall M, McConnell MJ, Jakhete N, Crismale J, Porges S, Khungar V, Mehta SJ, Goldberg D, Li Z, Schiano T, Regan L, Orloski C, Shea JA. Exploring opportunities to prevent cirrhosis admissions in the emergency department: A multicenter multidisciplinary survey. Hepatology Communications 2018, 2: 237-244. PMID: 29507899, PMCID: PMC5831018, DOI: 10.1002/hep4.1141.Peer-Reviewed Original ResearchEmergency departmentNonmedical factorsHepatic encephalopathyInpatient admissionsEmergency department observation unit protocolTriage decisionsLow-acuity casesLarge-volume paracentesisLiver transplant centersMild hepatic encephalopathyOutpatient specialty careEmergency medicine providersQuality improvement initiativesPatient-based scenariosCirrhosis admissionsReadmission ratesUnit protocolTransplant centersClinical presentationOutpatient settingPatient populationSpecialty careUnit visitsHepatology providersHigher admission
2017
Biology of portal hypertension
McConnell M, Iwakiri Y. Biology of portal hypertension. Hepatology International 2017, 12: 11-23. PMID: 29075990, PMCID: PMC7090883, DOI: 10.1007/s12072-017-9826-x.BooksMeSH KeywordsAnimalsAscitesBlood PlateletsEndothelial CellsEsophageal and Gastric VaricesFibrosisGastrointestinal HemorrhageHepatic EncephalopathyHepatic Veno-Occlusive DiseaseHepatorenal SyndromeHumansHypertension, PortalLiverMiceMicrovesselsModels, AnimalNeovascularization, PathologicRenal InsufficiencySplanchnic CirculationThrombosisVascular ResistanceConceptsLiver sinusoidal endothelial cellsPortal hypertensionMicrovascular thrombosisHepatic stellate cell activationHyperdynamic circulatory syndromeSystemic arterial vasodilationChronic liver diseaseIntrahepatic vascular resistanceSinusoidal portal hypertensionPortal hypertension resultsStellate cell activationSinusoidal endothelial cellsVascular biology researchHepatorenal syndromeGastroesophageal varicesVariceal hemorrhageVascular resistanceArterial vasodilationCirculatory syndromeRenal failureHepatic encephalopathyHypertension resultsLiver diseasePortosystemic shuntMesenteric vasculature
2012
Lipidomic discovery of deoxysiderophores reveals a revised mycobactin biosynthesis pathway in Mycobacterium tuberculosis.
Madigan CA, Cheng TY, Layre E, Young DC, McConnell MJ, Debono CA, Murry JP, Wei JR, Barry CE, Rodriguez GM, Matsunaga I, Rubin EJ, Moody DB. Lipidomic discovery of deoxysiderophores reveals a revised mycobactin biosynthesis pathway in Mycobacterium tuberculosis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 1257-62. PMID: 22232695, PMCID: PMC3268331, DOI: 10.1073/pnas.1109958109.Peer-Reviewed Original Research
2011
A comparative lipidomics platform for chemotaxonomic analysis of Mycobacterium tuberculosis.
Layre E, Sweet L, Hong S, Madigan CA, Desjardins D, Young DC, Cheng TY, Annand JW, Kim K, Shamputa IC, McConnell MJ, Debono CA, Behar SM, Minnaard AJ, Murray M, Barry CE, Matsunaga I, Moody DB. A comparative lipidomics platform for chemotaxonomic analysis of Mycobacterium tuberculosis. Chemistry & Biology 2011, 18: 1537-49. PMID: 22195556, PMCID: PMC3407843, DOI: 10.1016/j.chembiol.2011.10.013.Peer-Reviewed Original Research
2009
Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition.
Siegrist MS, Unnikrishnan M, McConnell MJ, Borowsky M, Cheng TY, Siddiqi N, Fortune SM, Moody DB, Rubin EJ. Mycobacterial Esx-3 is required for mycobactin-mediated iron acquisition. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 18792-7. PMID: 19846780, PMCID: PMC2774023, DOI: 10.1073/pnas.0900589106.Peer-Reviewed Original Research
2008
Mycolyltransferase-mediated glycolipid exchange in Mycobacteria.
Matsunaga I, Naka T, Talekar RS, McConnell MJ, Katoh K, Nakao H, Otsuka A, Behar SM, Yano I, Moody DB, Sugita M. Mycolyltransferase-mediated glycolipid exchange in Mycobacteria. The Journal Of Biological Chemistry 2008, 283: 28835-41. PMID: 18703502, PMCID: PMC2570876, DOI: 10.1074/jbc.M805776200.Peer-Reviewed Original Research