2015
A candidate gene study reveals association between a variant of the Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) gene and systemic sclerosis
Marangoni RG, Korman BD, Allanore Y, Dieude P, Armstrong LL, Rzhetskaya M, Hinchcliff M, Carns M, Podlusky S, Shah SJ, Ruiz B, Hachulla E, Tiev K, Cracowski JL, Varga J, Hayes MG. A candidate gene study reveals association between a variant of the Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) gene and systemic sclerosis. Arthritis Research & Therapy 2015, 17: 128. PMID: 25986483, PMCID: PMC4437446, DOI: 10.1186/s13075-015-0641-2.Peer-Reviewed Original ResearchConceptsSystemic sclerosisDiscovery cohortSingle nucleotide polymorphismsPathogenesis of SScNuclear receptor peroxisome proliferator-activated receptor gammaPeroxisome proliferator-activated receptor gammaPotent anti-fibrotic effectsPulmonary arterial hypertensionProliferator-activated receptor gammaAnti-fibrotic effectsRole of PPARGene single nucleotide polymorphismsReceptor gamma geneSSc cohortArterial hypertensionSSc patientsClinical parametersValidation cohortClinical associationsEuropean cohortReceptor gammaPPARG variantsDisease severityIntronic single nucleotide polymorphismC allele
2013
A synthetic PPAR-γ agonist triterpenoid ameliorates experimental fibrosis: PPAR-γ-independent suppression of fibrotic responses
Wei J, Zhu H, Komura K, Lord G, Tomcik M, Wang W, Doniparthi S, Tamaki Z, Hinchcliff M, Distler JH, Varga J. A synthetic PPAR-γ agonist triterpenoid ameliorates experimental fibrosis: PPAR-γ-independent suppression of fibrotic responses. Annals Of The Rheumatic Diseases 2013, 73: 446. PMID: 23515440, PMCID: PMC4028127, DOI: 10.1136/annrheumdis-2012-202716.Peer-Reviewed Original ResearchMeSH KeywordsAdipogenesisAdultAnimalsBiopsyCells, CulturedCollagenDisease Models, AnimalDrug Evaluation, PreclinicalFemaleFibroblastsFibrosisHumansInfant, NewbornMiceMice, Inbred C57BLOleanolic AcidOrgan Culture TechniquesPPAR gammaProto-Oncogene Proteins c-aktScleroderma, SystemicSignal TransductionSkinTransforming Growth Factor betaConceptsSkin organ cultureHuman skin organ cultureAntifibrotic effectsDermal fibrosisExperimental fibrosisOrgan culturePeroxisome proliferator-activated receptor γModulation of fibrogenesisProliferator-activated receptor γHuman skin equivalentsPotential new therapiesPotential therapeutic strategyFibrotic gene expressionSynthetic oleanane triterpenoidComplementary mouse modelsControl of fibrosisPersistent fibroblast activationGrowth factor βTGF-β signalingEffects of CDDOSystemic sclerosisBleomycin injectionFibrogenic responseFibrotic activityMurine model
2012
Levels of adiponectin, a marker for PPAR-gamma activity, correlate with skin fibrosis in systemic sclerosis: potential utility as biomarker?
Lakota K, Wei J, Carns M, Hinchcliff M, Lee J, Whitfield ML, Sodin-Semrl S, Varga J. Levels of adiponectin, a marker for PPAR-gamma activity, correlate with skin fibrosis in systemic sclerosis: potential utility as biomarker? Arthritis Research & Therapy 2012, 14: r102. PMID: 22548780, PMCID: PMC3446479, DOI: 10.1186/ar3827.Peer-Reviewed Original ResearchConceptsLevels of adiponectinPPAR-gamma activitySerum adiponectin levelsSystemic sclerosisAdiponectin levelsSkin fibrosisSSc patientsSkin scoreDiffuse cutaneous systemic sclerosisPeroxisome proliferator-activated receptor gammaCutaneous systemic sclerosisRodnan skin scoreProliferator-activated receptor gammaHuman subcutaneous preadipocytesProgression of fibrosisAdiponectin mRNA expressionAdiponectin gene expressionTransforming growth factor betaSignificant inverse correlationLongitudinal study changesGrowth factor betaProgressive fibrosisReal-time quantitative PCRAdiponectin expressionHealthy controls