Dataset Information

FoxO factors are necessary to maintain homeostasis in airway epithelial cells under stress situations

ABSTRACT: Airway epithelia must constantly cope with the difficult task of maintaining functional and structural homeostasis, even when exposed to various stress factors. Transcription factors of the FoxO family may play a crucial role in this process by responding to extrinsic and intrinsic factors and translating them into a physiologically relevant response. We could show that FoxO factors in Drosophila, mouse, and human AECs respond to stressors like hypoxia, temperature, or oxidative stress by nuclear translocation. Hypoxia stands out as it induces a FoxO-dependent activation of the immune response in the airways. In human cell culture systems, a complex activation pattern is revealed, which not only differs between individual FoxO factors but also between cell types. Transcriptome studies indicate that a lack of dFOXO activity is associated with increased stress sensitivity, as demonstrated in the simple Drosophila model. This stress sensitivity is also reflected in mouse models of chronic and acute asthma, in which reduced FoxO expression, particularly for FoxO1 and FoxO3A, is conspicuous. This is also reflected in asthma patients, who also show reduced FoxO transcripts in their sputum samples. We conclude that active FoxO signaling in AECs is necessary to respond appropriately to stressors and that a lack of FoxO signaling limits this ability and thus promotes disease.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE237586 | GEO | 2025/07/01

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Purpose: The goal of this RNA-Seq is to analyze the whole-body transcriptomes from normoxia vs hypoxia exposed flies to identify differentially expressed genes and to identify which differentially gene expression changes require the FOXO transcription factor Abstract from associated manuscript: When exposed to low oxygen or hypoxia, animals must alter their metabolism and physiology to ensure proper cell-, tissue- and whole-body level adaptations to their hypoxic environment. These alterations often involve changes in gene expression. While extensive work has emphasized the importance of the HIF-1 alpha transcription factor on controlling hypoxia gene expression, less is known about other transcriptional mechanisms. We previously identified the transcription factor FOXO as a regulator of hypoxia tolerance in Drosophila larvae and adults. Here we use an RNA sequencing approach to identify FOXO-dependent changes in gene expression that are associated with these tolerance effects. We found that hypoxia altered the expression of over 2000 genes and that approximately 40% of these gene expression changes required FOXO. We discovered that hypoxia exposure led to a FOXO-dependent increase in genes involved in cell signaling, such as kinases, GTPase regulators, and regulators of the Hippo/Yorkie pathway. Among these, we identified homeodomain-interacting protein kinase (Hipk) as being required for hypoxia survival. We also found that hypoxia suppresses the expression of genes involved in ribosome synthesis and egg production, and we showed that hypoxia suppresses tRNA synthesis and mRNA translation and reduces female fecundity. Among the downregulated genes, we discovered that FOXO was required for suppression of many ribosomal protein genes and genes involved in oxidative phosphorylation, pointing to a role for FOXO in limiting energetically costly processes such as protein synthesis and mitochondrial activity upon hypoxic stress. This work uncovers a widespread role for FOXO in mediating hypoxia changes in gene expression. Results: RNA Seq differential expression analysis identified a significant (p<0.05,> 1.5 fold expression) change in 2835 transcripts, with 1602 transcripts showing reduced expression levels and 1233 transcripts with elevated expression levels.

Dataset Information

FoxO factors are necessary to maintain homeostasis in airway epithelial cells under stress situations

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets