title: Genomic phenotype of non-cultured pulmonary fibroblasts in idiopathic pulmonary fibrosis.
abstract: Activated fibroblasts are the central effector cells of the progressive fibrotic process in idiopathic pulmonary fibrosis (IPF). Characterizing the genomic phenotype of isolated fibroblasts is essential to understanding IPF pathogenesis. Comparing the genomic phenotype of non-cultured pulmonary fibroblasts from advanced IPF patients' and normal lungs revealed novel genes, biological processes and concomitant pathways previously unreported in IPF fibroblasts. We demonstrate altered expression in proteasomal constituents, ubiquitination-mediators, Wnt, apoptosis and vitamin metabolic pathways and cell cycle regulators, suggestive of loss of cellular homeostasis. Specifically, FBXO32, CXCL14, BDKRB1 and NMNAT1 were up-regulated, while RARA and CDKN2D were down-regulated. Paradoxically, pro-apoptotic inducers TNFSF10, BAX and CASP6 were also found to be increased. This comprehensive description of altered gene expression in isolated IPF fibroblasts underscores the complex biological processes characteristic of IPF and may provide a foundation for future research into this devastating disease.
authors.affiliation: George Mason University, Department of Molecular and Microbiology, Manassas, VA 20110, USA.
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Emblom-Callahan
authors.forename: Mantej K
authors.initials: MK
authors.lastname: Chhina
authors.forename: Oksana A
authors.initials: OA
authors.lastname: Shlobin
authors.forename: Shahzad
authors.initials: S
authors.lastname: Ahmad
authors.forename: Erika S
authors.initials: ES
authors.lastname: Reese
authors.forename: Eswar P R
authors.initials: EP
authors.lastname: Iyer
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Cox
authors.forename: Renee
authors.initials: R
authors.lastname: Brenner
authors.forename: Nelson A
authors.initials: NA
authors.lastname: Burton
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: Grant
authors.forename: Steven D
authors.initials: SD
authors.lastname: Nathan
mesh_terms: D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D023281:Genomics; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics* / Q000503:physiopathology*; D008168:Lung / Q000166:cytology*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D018925:Chemokines; D016207:Cytokines