2023
Increased expression of CXCL6 in secretory cells drives fibroblast collagen synthesis and is associated with increased mortality in idiopathic pulmonary fibrosis.
Bahudhanapati H, Tan J, Apel R, Seeliger B, Schupp J, Li X, Sullivan D, Sembrat J, Rojas M, Tabib T, Valenzi E, Lafyatis R, Mitash N, Hernandez Pineda R, Jawale C, Peroumal D, Biswas P, Tedrow J, Adams T, Kaminski N, Wuyts W, McDyer J, Gibson K, Alder J, Königshoff M, Zhang Y, Nouraie M, Prasse A, Kass D. Increased expression of CXCL6 in secretory cells drives fibroblast collagen synthesis and is associated with increased mortality in idiopathic pulmonary fibrosis. European Respiratory Journal 2023, 63: 2300088. PMID: 37918852, DOI: 10.1183/13993003.00088-2023.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisAirway epithelial cellsBronchoalveolar lavagePulmonary fibrosisEpithelial cellsCollagen synthesisPathogenesis of IPFCohort of patientsIPF lung fibroblastsEffects of chemokinesAir-liquid interface culturesExpression of CXCL6Collagen I levelsIPF mortalityIPF patientsChemokine levelsIPF fibroblastsPoor survivalDistal lungI levelsWhole lungAnimal modelsEctopic localisationPatientsSingle-cell RNA sequencingmicroRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis
Ahangari F, Price N, Malik S, Chioccioli M, Bärnthaler T, Adams T, Kim J, Pradeep S, Ding S, Cosme C, Rose K, McDonough J, Aurelien N, Ibarra G, Omote N, Schupp J, DeIuliis G, Nunez J, Sharma L, Ryu C, Dela Cruz C, Liu X, Prasse A, Rosas I, Bahal R, Fernandez-Hernando C, Kaminski N. microRNA-33 deficiency in macrophages enhances autophagy, improves mitochondrial homeostasis, and protects against lung fibrosis. JCI Insight 2023, 8: e158100. PMID: 36626225, PMCID: PMC9977502, DOI: 10.1172/jci.insight.158100.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisPulmonary fibrosisMiR-33MiR-33 levelsSpecific genetic ablationBronchoalveolar lavage cellsNovel therapeutic approachesMitochondrial homeostasisFatty acid metabolismMacrophages protectsBleomycin injuryLavage cellsLung fibrosisHealthy controlsInflammatory responseTherapeutic approachesImmunometabolic responsesCholesterol effluxFibrosisFatal diseasePharmacological inhibitionSterol regulatory element-binding protein (SREBP) genesGenetic ablationMacrophagesEx vivo mouse
2022
Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis.
Ahangari F, Becker C, Foster DG, Chioccioli M, Nelson M, Beke K, Wang X, Justet A, Adams T, Readhead B, Meador C, Correll K, Lili LN, Roybal HM, Rose KA, Ding S, Barnthaler T, Briones N, DeIuliis G, Schupp JC, Li Q, Omote N, Aschner Y, Sharma L, Kopf KW, Magnusson B, Hicks R, Backmark A, Dela Cruz CS, Rosas I, Cousens LP, Dudley JT, Kaminski N, Downey GP. Saracatinib, a Selective Src Kinase Inhibitor, Blocks Fibrotic Responses in Preclinical Models of Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2022, 206: 1463-1479. PMID: 35998281, PMCID: PMC9757097, DOI: 10.1164/rccm.202010-3832oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisHuman precision-cut lung slicesPrecision-cut lung slicesPulmonary fibrosisNormal human lung fibroblastsEpithelial-mesenchymal transitionHuman lung fibroblastsFibrogenic pathwaysPreclinical modelsMurine modelLung slicesSrc kinase inhibitorLung fibroblastsKinase inhibitorsAmelioration of fibrosisSelective Src kinase inhibitorHuman lung fibrosisWhole lung extractsPotential therapeutic efficacyIPF diseaseIPF treatmentLung functionInflammatory cascadeLung fibrosisAntifibrotic efficacy