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Series GSE19362 Query DataSets for GSE19362
Status Public on Jul 22, 2011
Title Dissection of human fibroblast populations by lung regions: genomic differences and functional pathway analysis
Organism Homo sapiens
Experiment type Expression profiling by array
Summary ABSTRACT Background: Primary human distal lung/parenchymal fibroblasts (DLF) exhibit a different phenotype from airway fibroblasts (AF), including the expression of high levels of alpha-SMA. The scope of the differences and the mechanisms driving them are unknown. We hypothesized that the distinct fibroblast characteristics based on lung region predicted a broad range of genomic differences which contribute to distinctly different functional pathway activation in AF and DLF. Methods and Findings: To investigate whether comprehensive gene expression patterns vary between AF and DLF, we compared global gene expression profiles of 3 matched pairs of primary human fibroblasts isolated from proximal and distal lung. 194 transcripts were upregulated in AF, and 290 transcripts upregulated in DLF. Quantitative real-time PCR (qRT-PCR) from both asthmatic and normal subjects confirmed the validity of microarray data (n = 8). Further analysis identified distinct pathway activation patterns, including the identification of the TGF-β receptor/SMAD3 signaling pathway as critical to the phenotypic differences in AF and DLF. The functional impact of these molecular differences on AF and DLF was then analyzed using Western blot, qRT-PCR, ELISA and gene knock-down approaches. TGF-β receptor/SMAD2-3 pathway analysis confirmed the contribution of higher TGF-β1 expression and accompanying SMAD3 and JNK activation to the increased alpha-SMA level seen in DLF. There are two limitations associated with our work. First, the microarray sample size was small. Second, for ethical reasons, a large majority of our data were from asthmatic subjects, only one pair of airway and distal lung tissues from a subject without knowing preexisting lung disease matched for age and smoking status was available. In this single normal subject, the same pattern of differences existed, supporting the concept that these genomic differences are regional, rather than disease-related. Conclusions: These findings demonstrated marked molecular and functional differences for these two lung regional fibroblast populations. These results suggest that airway and parenchymal fibroblasts differ in their responses to injury, repair, and remodeling in the lungs. There are likely profound implications of these observations for understanding mechanisms of development of fibrotic lung diseases as well as approaching therapy.
Overall design In order to identify the underlying molecular differences between airway- and distal lung fibroblasts, microarray analysis was performed on 3 different matched pairs of fibroblasts.
Contributor(s) Zhou X, Wu W, Hu H, Milosevic J, Konishi K, Kaminski N, Wenzel SE
Citation(s) 21757679
Submission date Dec 07, 2009
Last update date Feb 22, 2018
Contact name XIUXIA ZHOU
Phone 412-692-4156
Fax 412-692-2260
Organization name University of Pittsburgh
Department Medicine
Lab Sally E. Wenzel
Street address 3459 fifth ave
City Pittsburgh
State/province PA
ZIP/Postal code 15213
Country USA
Platforms (1)
GPL4133 Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version)
Samples (6)
GSM480652 AirwayFibroblast_0349Q
GSM480653 DistalLungFibroblast_0349Q
GSM480654 AirwayFibroblast_0944E
BioProject PRJNA120397

Download family Format
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE19362_RAW.tar 53.7 Mb (http)(custom) TAR (of TXT)
Processed data included within Sample table

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