2024
Targeting hypoxia and thrombospondin‐2 in diabetic wound healing
Huang Y, Xing H, Naud S, Kyriakides T. Targeting hypoxia and thrombospondin‐2 in diabetic wound healing. The FASEB Journal 2024, 38: e70091. PMID: 39383062, PMCID: PMC11486302, DOI: 10.1096/fj.202302429rrr.Peer-Reviewed Original ResearchConceptsThrombospondin-2Diabetic miceWound healingHIF-1aMatricellular protein thrombospondin-2Diabetic woundsImpaired wound healingWounds of diabetic miceDimethyloxalylglycine treatmentTargeting hypoxiaSustained hypoxiaDiabetic patientsTSP2 expressionCell dysfunctionIncreased neovascularizationDiabetic wound healingGenetic ablationDiabetic fibroblastsElevated glucoseReduced hypoxiaImprove healingImmunofluorescence analysisHIF-1a activationHypoxiaWestern blotting
2022
Dysregulation of TSP2-Rac1-WAVE2 axis in diabetic cells leads to cytoskeletal disorganization, increased cell stiffness, and dysfunction
Xing H, Huang Y, Kunkemoeller B, Dahl P, Muraleetharan O, Malvankar N, Murrell M, Kyriakides T. Dysregulation of TSP2-Rac1-WAVE2 axis in diabetic cells leads to cytoskeletal disorganization, increased cell stiffness, and dysfunction. Scientific Reports 2022, 12: 22474. PMID: 36577792, PMCID: PMC9797577, DOI: 10.1038/s41598-022-26337-1.Peer-Reviewed Original ResearchConceptsCell-derived matricesCell stiffnessFamily verprolin-homologous protein 2Active Rac1Thrombospondin-2Homologous protein 2Less traction forceCytoskeleton organizationExtracellular matrix productionMajor cell populationF-actinCytoskeletal disorganizationRegulatory roleProtein 2Matrix productionCritical functionsECM productionArt microscopy techniquesNew functionsCell populationsSpindle-like shapeRac1Normal fibroblastsFibroblastsWound space
2019
Elevated Thrombospondin 2 Contributes to Delayed Wound Healing in Diabetes
Kunkemoeller B, Bancroft T, Xing H, Morris AH, Luciano AK, Wu J, Fernandez-Hernando C, Kyriakides TR. Elevated Thrombospondin 2 Contributes to Delayed Wound Healing in Diabetes. Diabetes 2019, 68: 2016-2023. PMID: 31391172, PMCID: PMC6754242, DOI: 10.2337/db18-1001.Peer-Reviewed Original ResearchConceptsThrombospondin-2TSP2 expressionDiabetic control miceWound healingEffects of hyperglycemiaImpaired wound healingUnderlying pathological mechanismsDelayed Wound HealingMajor cellular sourceBlood vessel maturationGranulation tissue formationMajor complicationsDiabetic miceControl miceTreatment strategiesDiabetesPathological mechanismsDiabetic woundsAccelerated reepithelializationCellular sourceHigh glucoseHyperglycemiaMatricellular proteinExpression contributesHexosamine pathwayThrombospondin-2 regulates extracellular matrix production, LOX levels, and cross-linking via downregulation of miR-29
Calabro NE, Barrett A, Chamorro-Jorganes A, Tam S, Kristofik NJ, Xing H, Loye AM, Sessa WC, Hansen K, Kyriakides TR. Thrombospondin-2 regulates extracellular matrix production, LOX levels, and cross-linking via downregulation of miR-29. Matrix Biology 2019, 82: 71-85. PMID: 30876926, PMCID: PMC6710120, DOI: 10.1016/j.matbio.2019.03.002.Peer-Reviewed Original ResearchConceptsECM protein productionProtein productionLysyl oxidaseThrombospondin-2MiR-29Matricellular proteinQuantitative proteomics approachLevels of LOXExtracellular matrix productionProteomic approachECM proteinsMajor regulatorECM homeostasisExtracellular matrixMatrix productionProteinCollagen fibrillogenesisMiR-29 expressionFibrillar collagenImportant modulatorDependent processesLOX levelsRegulatorProductionHomeostasis