2015
The Histone Deacetylase Sirtuin 1 Is Reduced in Systemic Sclerosis and Abrogates Fibrotic Responses by Targeting Transforming Growth Factor β Signaling
Wei J, Ghosh AK, Chu H, Fang F, Hinchcliff ME, Wang J, Marangoni RG, Varga J. The Histone Deacetylase Sirtuin 1 Is Reduced in Systemic Sclerosis and Abrogates Fibrotic Responses by Targeting Transforming Growth Factor β Signaling. Arthritis & Rheumatology 2015, 67: 1323-1334. PMID: 25707573, PMCID: PMC4518870, DOI: 10.1002/art.39061.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCase-Control StudiesCells, CulturedDisease Models, AnimalEnzyme InhibitorsFibroblastsHumansMiceP300-CBP Transcription FactorsPlatelet-Derived Growth FactorReal-Time Polymerase Chain ReactionResveratrolRNA, MessengerScleroderma, SystemicSignal TransductionSirtuin 1SkinSmad ProteinsStilbenesTransforming Growth Factor betaConceptsGenome-wide expression data setsTransforming Growth Factor β SignalingGrowth factor β signalingSSc skin biopsy samplesSirtuin 1Histone deacetylase sirtuin 1Tissue expressionExpression data setsPlatelet-derived growth factorTranscriptome dataDeacetylase sirtuin 1Epigenetic mechanismsAcetyltransferase p300Acetylation statusEnzyme sirtuin 1Persistent fibroblast activationEffect of SIRT1Β signalingMessenger RNA levelsMouse fibroblastsFibrotic responseLoss of SIRT1Activation of SIRT1Pharmacologic inhibitionExperimental fibrosis model
2013
Early Growth Response 3 (Egr-3) Is Induced by Transforming Growth Factor-β and Regulates Fibrogenic Responses
Fang F, Shangguan AJ, Kelly K, Wei J, Gruner K, Ye B, Wang W, Bhattacharyya S, Hinchcliff ME, Tourtellotte WG, Varga J. Early Growth Response 3 (Egr-3) Is Induced by Transforming Growth Factor-β and Regulates Fibrogenic Responses. American Journal Of Pathology 2013, 183: 1197-1208. PMID: 23906810, PMCID: PMC3791870, DOI: 10.1016/j.ajpath.2013.06.016.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnimalsDisease Models, AnimalEarly Growth Response Protein 1Early Growth Response Protein 2Early Growth Response Protein 3FemaleFibroblastsFibrosisGene Expression ProfilingGene Expression RegulationHumansIntracellular SpaceMaleMiceMice, Inbred BALB CMiddle AgedScleroderma, SystemicSignal TransductionSkinSmad ProteinsTransforming Growth Factor betaConceptsEgr-3Genome-wide expression profilingSubstantial functional divergenceEarly growth response (EGR) gene familyEarly growth response 3Egr family membersFunctional divergenceGene familyFibroblast genesGrowth factorTranscription factorsExpression profilingBiological functionsGene expressionDistinct membersEgr familyEgr-1Canonical Smad3Distinct rolesEgr-2Normal skin fibroblastsTissue remodelingFibrotic gene expressionGenesFirst evidence
2012
Wnt/β‐catenin signaling is hyperactivated in systemic sclerosis and induces Smad‐dependent fibrotic responses in mesenchymal cells
Wei J, Fang F, Lam AP, Sargent JL, Hamburg E, Hinchcliff ME, Gottardi CJ, Atit R, Whitfield ML, Varga J. Wnt/β‐catenin signaling is hyperactivated in systemic sclerosis and induces Smad‐dependent fibrotic responses in mesenchymal cells. Arthritis & Rheumatism 2012, 64: 2734-2745. PMID: 22328118, PMCID: PMC3553791, DOI: 10.1002/art.34424.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultBeta CateninBiopsyCase-Control StudiesCell MovementCell ProliferationCells, CulturedFibroblastsFibrosisFrizzled ReceptorsHumansIntercellular Signaling Peptides and ProteinsLymphoid Enhancer-Binding Factor 1MesodermRepressor ProteinsScleroderma, SystemicSignal TransductionSkinSmad ProteinsWnt ProteinsWnt3A ProteinConceptsWnt/β-cateninCanonical WntWnt-3aMesenchymal cellsGenome-wide expression dataAberrant Wnt/β-catenin pathway activationCell fate specificationΒ-cateninSkin biopsy specimensMyofibroblast differentiationCanonical Wnt/β-cateninWnt/β-catenin signalingWnt receptor Fzd2Subcutaneous preadipocytesSystemic sclerosisΒ-catenin signalingFate specificationBiopsy specimensΒ-catenin activationExpression of WntHuman mesenchymal cellsGrowth factor βPathway componentsGene expressionProfibrotic responses
2007
Connective tissue growth factor/CCN2-null mouse embryonic fibroblasts retain intact transforming growth factor-β responsiveness
Mori Y, Hinchcliff M, Wu M, Warner-Blankenship M, Lyons K, Varga J. Connective tissue growth factor/CCN2-null mouse embryonic fibroblasts retain intact transforming growth factor-β responsiveness. Experimental Cell Research 2007, 314: 1094-1104. PMID: 18201696, PMCID: PMC3963386, DOI: 10.1016/j.yexcr.2007.12.010.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell DifferentiationCell ProliferationCells, CulturedCollagenCollagen Type IConnective Tissue Growth FactorEmbryo, MammalianExtracellular MatrixFibroblastsFibrosisGene ExpressionImmediate-Early ProteinsIntercellular Signaling Peptides and ProteinsMiceSignal TransductionSmad ProteinsTransforming Growth Factor betaConceptsEmbryonic fibroblastsSmad-dependent transcriptional responsesTGF-beta signal transductionMatricellular protein connective tissue growth factorMurine embryonic fibroblastsMouse embryonic fibroblastsProtein connective tissue growth factorWild-type MEFsTransient transfection assaysMyofibroblast transdifferentiationCCN2 expressionRegulation of proliferationCorresponding protein levelsCCN2 functionsCollagen gene expressionTranscriptional responseRT-PCR analysisLoss of CCN2Signal transductionEndogenous CCN2Transfection assaysExtracellular matrix synthesisMouse embryosGene expressionWild type