Unknown,Transcriptomics,Genomics,Proteomics

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Mechanisms of TGFB1 induced atrial fibrosis

ABSTRACT: This project aims to compare gene expression in transgenic mice that overexpress TGFB1 to wild type mice. Transgenic mice have a fibrotic response in the atria, but not the ventricle. This is a 2 color design; dye swaps and a loop design were incorporated. Each group has N=4, with the exception being WT atria which has N=3 and was hybridied twice, the groups are Wt atria, WT ventricle, Transgenic atria, Transgenic ventricle. Comparisons of interest : Tg atria vs WT atria, Tg ventricle vs WT ventricle, WT atria vs.dWT ventricle, Tg atria vs Tg ventricle

ORGANISM(S): Mus musculus

SUBMITTER: Andrea Barczak

PROVIDER: E-GEOD-27133 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Scnn1b-Tg mice overexpress the beta subunit of the epithelial sodium channel (Scnn1b) in airway Club cells. The general phenotype of these mice is described in three published manuscripts (Mall et al. 2004, Nature Medicine, 10(5):487-93; Mall et al. 2008, Am J Respir Crit Care Med. 177(7):730-42; Livraghi-Butrico et al. 2012, Physiol. Genomics 44(8):470-84; and Livraghi-Butrico et al. 2012, Mucosal Immunology 5(4):397-408). Briefly, overexpression of the Scnn1b transgene in airway Club cells leads to hyperabsorption of sodium from the airway surface liquid, which causes airway surface liquid and mucus dehydration, resulting in reduced mucus clearance and airway mucus obstruction. The data provided here represents mRNA expression data from disseccted whole lung from male WT and Scnn1b-transgenic littermates (C57Bl/6NTac background) at 4 time points [postnatal days (PND) 0, 3, 10, and 42]. Histologically, PND 0 lungs are normal, at PND 3 the intrapulmonary airways exhibit transient and spotty Club cell necrosis, and by PND 10 airway mucus obstruction is evident in the proximal portion of the intrapulmonary main stem bronchus. At PND 42, Scnn1b-Tg lungs are charactyerized by chronic low level inflammation, with activated macrophages, neutrophilia, eosinophilia and increased incidence of bronchus-associated lymphoid tissue. The data from the WT mice provides a global look at mRNA post-natal developmental changes, while the data from the Scnn1b-transgenic line allows differential gene expression due to airway surface liquid dehydration and mucus obstruction to be queried. The data presented for the lung is part of a larger body of work evaluating gene expression in lung (left lobe only), trachea, and purified macrophages (from bronchoalveolar lavage fluid). 24 Total lung (left lobe only) samples were analyzed; three from each timepoint for each genotype (wild type and Scnn1b-transgenic). In our manuscript, we were most interested in changes between WT and Scnn1b-Tg mice, however, the data can also be used to evaluate changes in gene expression across time (PND 0, 3, 10, and 42). We generated the following pairwise comparisons: Scnn1b-Tg vs WT mice for each PND time point; Intra-strain comparison between PND 3, or 10, or 42 vs PND 0.

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Mechanisms of TGFB1 induced atrial fibrosis

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