Genomic phenotype of non-cultured pulmonary fibroblasts in idiopathic pulmonary fibrosis
Autor: | Oksana A. Shlobin, Daniel N. Cox, Nelson A. Burton, Renee Brenner, Margaret C. Emblom-Callahan, Eswar Prasad Ramachandran Iyer, Geraldine Grant, Erika S. Reese, Mantej K. Chhina, Shahzad Ahmad, Steven D. Nathan |
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Rok vydání: | 2010 |
Předmět: |
Blotting
Western Cellular homeostasis Apoptosis Microarray Biology Pathogenesis Idiopathic pulmonary fibrosis Pulmonary fibrosis Genetics medicine Humans CXCL14 Lung Oligonucleotide Array Sequence Analysis Regulation of gene expression Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Cell Cycle Wnt signaling pathway Genomics Fibroblasts respiratory system medicine.disease Phenotype Idiopathic Pulmonary Fibrosis humanities respiratory tract diseases Gene Expression Regulation Immunology Fibroblast Cytokines Chemokines Signal Transduction |
Zdroj: | Genomics. 96:134-145 |
ISSN: | 0888-7543 |
DOI: | 10.1016/j.ygeno.2010.04.005 |
Popis: | 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. |
Databáze: | OpenAIRE |
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