2022
Deletion of LDLRAP1 Induces Atherosclerotic Plaque Formation, Insulin Resistance, and Dysregulated Insulin Response in Adipose Tissue
Leigh T, Kawai T, Preston K, Kelemen S, Okune R, St Paul A, Corbett C, Peluzzo A, Yu J, Scalia R, Autieri M. Deletion of LDLRAP1 Induces Atherosclerotic Plaque Formation, Insulin Resistance, and Dysregulated Insulin Response in Adipose Tissue. American Journal Of Pathology 2022, 192: 1092-1108. PMID: 35460615, PMCID: PMC9253916, DOI: 10.1016/j.ajpath.2022.03.014.Peer-Reviewed Original ResearchConceptsLow density lipoprotein receptor adaptor protein 1Visceral adipose tissueInsulin resistanceAdipose tissueAdaptor protein 1Metabolic regulatory rolesHigh-fat Western dietComorbidities of obesityWild-type controlsGene expression signaturesIncreased plasma cholesterolReduced glucose uptakeIncreased CD36 expressionIncreased plaque burdenPreclinical modelsLipid storageChow dietRegulatory roleVascular inflammationCD36 expressionWestern dietAtherosclerotic plaque formationMetabolic profileAkt phosphorylationEnergy homeostasis
2020
Interleukin 35 Delays Hindlimb Ischemia-Induced Angiogenesis Through Regulating ROS-Extracellular Matrix but Spares Later Regenerative Angiogenesis
Fu H, Sun Y, Shao Y, Saredy J, Cueto R, Liu L, Drummer C, Johnson C, Xu K, Lu Y, Li X, Meng S, Xue E, Tan J, Jhala N, Yu D, Zhou Y, Bayless K, Yu J, Rogers T, Hu W, Snyder N, Sun J, Qin X, Jiang X, Wang H, Yang X. Interleukin 35 Delays Hindlimb Ischemia-Induced Angiogenesis Through Regulating ROS-Extracellular Matrix but Spares Later Regenerative Angiogenesis. Frontiers In Immunology 2020, 11: 595813. PMID: 33154757, PMCID: PMC7591706, DOI: 10.3389/fimmu.2020.595813.Peer-Reviewed Original ResearchConceptsReactive oxygen speciesIL-35Ischemia-induced angiogenesisHindlimb ischemiaOmics data analysisApoE-/- controlsLoss-of-functionEndothelial cellsExtracellular matrix remodeling proteinsRegenerative angiogenesisExtracellular matrix proteinsGain-of-functionRNA-seqExtracellular matrix re-organizationIL-6STMatrix remodeling proteinsTranscriptome analysisLate phaseTube formation <i>IL-12RB2Interleukin (ILTranscriptome analysis of endothelial cellsIL-12 familyMatrix proteinsAnalysis of endothelial cellsAn allosteric site on MKP5 reveals a strategy for small-molecule inhibition
Gannam Z, Min K, Shillingford SR, Zhang L, Herrington J, Abriola L, Gareiss PC, Pantouris G, Tzouvelekis A, Kaminski N, Zhang X, Yu J, Jamali H, Ellman JA, Lolis E, Anderson KS, Bennett AM. An allosteric site on MKP5 reveals a strategy for small-molecule inhibition. Science Signaling 2020, 13 PMID: 32843541, PMCID: PMC7569488, DOI: 10.1126/scisignal.aba3043.Peer-Reviewed Original ResearchMeSH KeywordsAllosteric SiteAmino Acid SequenceAnimalsCell DifferentiationCell LineDual-Specificity PhosphatasesEnzyme InhibitorsFemaleHigh-Throughput Screening AssaysHumansKineticsMiceMice, KnockoutMitogen-Activated Protein Kinase PhosphatasesMyoblastsProtein BindingSequence Homology, Amino AcidSignal TransductionSmall Molecule LibrariesConceptsDystrophic muscle diseaseMitogen-activated protein kinaseMuscle diseaseTGF-β1Promising therapeutic targetP38 mitogen-activated protein kinaseTherapeutic strategiesTherapeutic targetSmall molecule inhibitionSmad2 phosphorylationDiseasePotential targetSmall-molecule screenInhibitorsTreatmentInhibition