Ubiquitination of ATF6 by disease-associated RNF186 promotes the innate receptor-induced unfolded protein response
Ranjan K, Hedl M, Sinha S, Zhang X, Abraham C. Ubiquitination of ATF6 by disease-associated RNF186 promotes the innate receptor-induced unfolded protein response. Journal Of Clinical Investigation 2021, 131: e145472. PMID: 34623328, PMCID: PMC8409591, DOI: 10.1172/jci145472.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 6AnimalsEndoplasmic Reticulum StressGenetic VariationHost Microbial InteractionsHumansImmunity, InnateInflammatory Bowel DiseasesMacrophagesMiceMice, Inbred C57BLMice, KnockoutNod2 Signaling Adaptor ProteinReceptors, Pattern RecognitionRisk FactorsSignal TransductionUbiquitinationUbiquitin-Protein LigasesUnfolded Protein ResponseConceptsPattern recognition receptorsUnfolded protein responseInflammatory bowel diseaseER stress sensorsHuman macrophagesIntestinal immune homeostasisProtein responseInnate immune systemRisk variantsKey macrophage functionsBowel diseaseOral challengeTranscription factor 6Immune homeostasisCytokine secretionColonic tissueMacrophage functionStress sensorImmune systemRecognition receptorsEffective clearanceMicrobial responsesWeight lossMacrophagesUbiquitinationLiver 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 antigenEndotheliopathyPatientsInjury