1. Genomic phenotype of non-cultured pulmonary fibroblasts in idiopathic pulmonary fibrosis.
- Author
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Emblom-Callahan MC, Chhina MK, Shlobin OA, Ahmad S, Reese ES, Iyer EP, Cox DN, Brenner R, Burton NA, Grant GM, and Nathan SD
- Subjects
- Apoptosis genetics, Blotting, Western, Cell Cycle genetics, Chemokines metabolism, Cytokines metabolism, Gene Expression Profiling, Genomics, Humans, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, Fibroblasts metabolism, Gene Expression Regulation physiology, Idiopathic Pulmonary Fibrosis genetics, Idiopathic Pulmonary Fibrosis physiopathology, Lung cytology, Phenotype, Signal Transduction physiology
- 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.
- Published
- 2010
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