2020
Cathepsin B promotes collagen biosynthesis, which drives bronchiolitis obliterans syndrome
Morrone C, Smirnova NF, Jeridi A, Kneidinger N, Hollauer C, Schupp JC, Kaminski N, Jenne D, Eickelberg O, Yildirim AÖ. Cathepsin B promotes collagen biosynthesis, which drives bronchiolitis obliterans syndrome. European Respiratory Journal 2020, 57: 2001416. PMID: 33303550, DOI: 10.1183/13993003.01416-2020.Peer-Reviewed Original ResearchConceptsBronchoalveolar lavage fluidCathepsin B activityHealthy donorsLung tissueCollagen depositionB activityCathepsin BBronchiolitis obliterans syndromeProgression of BOSFluorescence resonance energy transfer-based assayPromising therapeutic targetGrowth factor-β1Cathepsin B levelsSubsequent collagen depositionBOS pathogenesisBOS patientsBOS progressionLTx patientsLymphocytic bronchiolitisObliterans syndromeLung transplantationPeribronchial fibrosisPulmonary dysfunctionLung functionMajor complicationsAn 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
2017
Integrin alpha 11 in the regulation of the myofibroblast phenotype: implications for fibrotic diseases
Bansal R, Nakagawa S, Yazdani S, van Baarlen J, Venkatesh A, Koh AP, Song WM, Goossens N, Watanabe H, Beasley MB, Powell CA, Storm G, Kaminski N, van Goor H, Friedman SL, Hoshida Y, Prakash J. Integrin alpha 11 in the regulation of the myofibroblast phenotype: implications for fibrotic diseases. Experimental & Molecular Medicine 2017, 49: e396-e396. PMID: 29147013, PMCID: PMC5704196, DOI: 10.1038/emm.2017.213.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationDisease Models, AnimalFibrosisGene Expression RegulationGene Knockdown TechniquesHedgehog ProteinsHepatic Stellate CellsHumansImmunohistochemistryIntegrin alpha ChainsKidney DiseasesLiver CirrhosisMiceMyofibroblastsPhenotypeSignal TransductionTransforming Growth Factor betaConceptsHepatic stellate cellsFibrotic parametersMouse modelStellate cellsTissue fibrosisIntegrin alpha 11Alpha 11Smooth muscle actin-positive myofibroblastsLiver fibrosis mouse modelHuman hepatic stellate cellsMyofibroblast phenotypeFibrosis mouse modelPromising therapeutic targetActin-positive myofibroblastsCause of mortalityGrowth factor βAberrant extracellular matrixImpaired contractilityFibrogenic signalingFibrotic organsFibrogenic processExtracellular matrixTherapeutic targetOrgan fibrosisMyofibroblastic differentiation