2016
Tenascin-C drives persistence of organ fibrosis
Bhattacharyya S, Wang W, Morales-Nebreda L, Feng G, Wu M, Zhou X, Lafyatis R, Lee J, Hinchcliff M, Feghali-Bostwick C, Lakota K, Budinger GR, Raparia K, Tamaki Z, Varga J. Tenascin-C drives persistence of organ fibrosis. Nature Communications 2016, 7: 11703. PMID: 27256716, PMCID: PMC4895803, DOI: 10.1038/ncomms11703.Peer-Reviewed Original ResearchConceptsSystemic sclerosisToll-like receptorsOrgan fibrosisFibrosis resolutionPathogenesis of SScTreatment of SScLevels of tenascinEndogenous danger signalsSSc skin biopsy samplesSkin biopsy samplesMechanism of actionLung fibrosisPathogenic roleTLR activatorsMouse modelBiopsy samplesFibroblast activationDanger signalsMyofibroblast transformationFibrosisSSc fibroblastsCollagen gene expressionSkin fibroblastsAmplification loopTenascin
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