Genomic differences distinguish the myofibroblast phenotype of distal lung from airway fibroblasts
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ABSTRACT: ABSTRACT Primary human distal lung/parenchymal fibroblasts (DLF) exhibit a different phenotype from airway fibroblasts (AF), including the expression of high levels of a-smooth muscle actin (a-SMA). The scope of the differences and the mechanisms driving them are unknown. To determine whether distinct fibroblast characteristics and function based on lung region are predicted by a broad range of genomic differences in AF vs DLF. Matched human fibroblast pairs isolated from proximal and distal lung in 18 asthmatic and 4 normal subjects were studied. Microarray analysis was performed on 12 matched fibroblast pairs (8 asthmatic and 4 normal subjects) and validated by quantitative real-time PCR (qRT-PCR). The functional impact of these molecular differences on AF and DLF was then revealed using computational approaches. Microarray data demonstrated 474 transcripts upregulated in AF, and 611 transcripts upregulated in DLF, when the asthmatic and normal fibroblasts were combined for all the analysis. Further gene ontology (GO) and network analysis identified distinct pathway activation patterns between AF and DLF, including identification of the SMAD3 and MAPK8 signaling pathways. These results demonstrated that marked molecular and functional differences exist between these two lung regional fibroblast populations. These striking differences identify multiple potential mechanisms by which AF and DLF differ in their responses to injury, regeneration and remodeling in the lungs.
ORGANISM(S): Homo sapiens
PROVIDER: GSE27335 | GEO | 2011/07/22
SECONDARY ACCESSION(S): PRJNA137313
REPOSITORIES: GEO
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