Activation of SREBP in Alveolar Type II Cells Enhances Lipogenesis Causing Pulmonary Lipotoxicity
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE31797 | GEO | 2012/03/01
SECONDARY ACCESSION(S): PRJNA145471
REPOSITORIES: GEO
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Project description:Background: Lung function is dependent upon the precise regulation of the synthesis, storage, and catabolism of tissue and alveolar lipids. Results: Activation of SREBP (Sterol Response Element Binding Protein) induced lipogenesis in alveolar epithelial cells, causing neutral lipid accumulation, lung inflammation, and tissue remodeling. Conclusions: The accumulation of neutral lipids in type II epithelial cells and alveolar macrophages caused lung inflammation, consistent with findings in lipid storage disorders. Significance: Pulmonary lipotoxicity may contribute to the pathogenesis of lung dysfunction associated with diabetes, obesity, and other metabolic disorders. Genome-wide transcription profiling comparison between doxycycline-exposed SFTPC-rtTAWT/Tg/(tetO)7CMV-CreWT/Tg/Insig1flox/flox/Insig2-/- mice (i.e., Insig1/2∆/∆ ) and Insig1flox/flox/Insig2-/- . Three independent pooled RNA from isolated lung type 2 cells of each genotype were used.
2012-03-01 | E-GEOD-31797 | biostudies-arrayexpress
Project description:Pulmonary function after birth is dependent upon surfactant lipids that reduce surface tension in the alveoli. The sterol-responsive element-binding proteins (SREBPs) are transcription factors regulating expression of genes controlling lipid homeostasis in many tissues. To identify the role of SREBPs in the lung, we conditionally deleted the SREBP cleavage-activating protein gene, Scap, in respiratory epithelial cells (Scap∆/∆) in vivo. Prior to birth (E18.5), deletion of Scap decreased the expression of both SREBPs and a number of genes regulating fatty acid and cholesterol metabolism. Nevertheless, Scap∆/∆ mice survived postnatally, surfactant and lung tissue lipids being substantially normalized in adult Scap∆/∆ mice. Although phospholipid synthesis was decreased in type II cells from adult Scap∆/∆ mice, lipid storage, synthesis, and transfer by lung lipofibroblasts were increased. mRNA microarray data indicated that SCAP influenced two major gene networks, one regulating lipid metabolism and the other stress-related responses. Deletion of the SCAP/SREBP pathway in respiratory epithelial cells altered lung lipid homeostasis and induced compensatory lipid accumulation and synthesis in lung lipofibroblasts. To identify the role of SREBPs in the lung, we conditionally deleted the SREBP cleavage-activating protein gene, Scap, in respiratory epithelial cells (Scap∆/∆) in vivo.Lung cRNA was hybridized to the murine genome MOE430 V2 chips.
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Project description:Pulmonary function after birth is dependent upon surfactant lipids that reduce surface tension in the alveoli. The sterol-responsive element-binding proteins (SREBPs) are transcription factors regulating expression of genes controlling lipid homeostasis in many tissues. To identify the role of SREBPs in the lung, we conditionally deleted the SREBP cleavage-activating protein gene, Scap, in respiratory epithelial cells (Scap∆/∆) in vivo. Prior to birth (E18.5), deletion of Scap decreased the expression of both SREBPs and a number of genes regulating fatty acid and cholesterol metabolism. Nevertheless, Scap∆/∆ mice survived postnatally, surfactant and lung tissue lipids being substantially normalized in adult Scap∆/∆ mice. Although phospholipid synthesis was decreased in type II cells from adult Scap∆/∆ mice, lipid storage, synthesis, and transfer by lung lipofibroblasts were increased. mRNA microarray data indicated that SCAP influenced two major gene networks, one regulating lipid metabolism and the other stress-related responses. Deletion of the SCAP/SREBP pathway in respiratory epithelial cells altered lung lipid homeostasis and induced compensatory lipid accumulation and synthesis in lung lipofibroblasts.
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