Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis
Chandran RR, Xie Y, Gallardo-Vara E, Adams T, Garcia-Milian R, Kabir I, Sheikh AQ, Kaminski N, Martin KA, Herzog EL, Greif DM. Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis. Nature Communications 2021, 12: 7179. PMID: 34893592, PMCID: PMC8664937, DOI: 10.1038/s41467-021-27499-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationDisease Models, AnimalDown-RegulationExtracellular MatrixFemaleFibroblastsFibrosisHumansKruppel-Like Factor 4LungLung InjuryMaleMesenchymal Stem CellsMiceMice, Inbred C57BLMyofibroblastsReceptor, Platelet-Derived Growth Factor betaRespiratory Tract DiseasesSignal TransductionTransforming Growth Factor betaConceptsMesenchymal cell typesPlatelet-derived growth factor receptorSmooth muscle actinLung fibrosisKruppel-like factor 4Forkhead box M1Growth factor receptorCell transitionCell typesExtracellular matrixDistinct rolesKLF4Box M1C chemokine ligandMesenchymal cell subtypesFactor receptorPro-fibrotic effectsFactor 4PDGFRMesenchymeCellsMacrophage accumulationKLF4 levelsChemokine ligandLung fibrogenesisMacrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis
Gao R, Peng X, Perry C, Sun H, Ntokou A, Ryu C, Gomez JL, Reeves BC, Walia A, Kaminski N, Neumark N, Ishikawa G, Black KE, Hariri LP, Moore MW, Gulati M, Homer RJ, Greif DM, Eltzschig HK, Herzog EL. Macrophage-derived netrin-1 drives adrenergic nerve–associated lung fibrosis. Journal Of Clinical Investigation 2021, 131: e136542. PMID: 33393489, PMCID: PMC7773383, DOI: 10.1172/jci136542.Peer-Reviewed Original ResearchConceptsNetrin-1Lung fibrosisCell-specific knockout miceΑ1-adrenoreceptor blockadeIPF lung tissueNeuronal guidance proteinsNetrin-1 expressionExtracellular matrix accumulationAdrenergic processesAdrenoreceptor antagonismAdrenoreceptor blockadeFibrotic histologyInflammatory scarringIPF cohortAdrenergic nervesΑ1-blockersImproved survivalColorectal carcinomaLung tissueKnockout miceCollagen accumulationFibrosisMatrix accumulationMacrophagesGuidance proteins