Hypercapnia Alters Expression of Immune Response, Nucleosome Assembly and Lipid Metabolism Genes in Differentiated Human Bronchial Epithelial Cells
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PROVIDER: PRJNA433531 | ENA |
REPOSITORIES: ENA
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Project description:Hypercapnia, the elevation of CO2 in blood and tissues, commonly occurs in severe acute and chronic respiratory diseases, and is associated with increased risk of mortality. Recent studies have shown that hypercapnia adversely affects innate immunity, host defense, lung edema clearance, and cell proliferation. Airway epithelial dysfunction is a feature of advanced lung disease, but the effect of hypercapnia on airway epithelium is unknown. Thus, in the current study we examined the effect of normoxic hypercapnia (20% CO2 for 24 h) vs normocapnia (5% CO2), on global gene expression in differentiated normal human airway epithelial cells. Gene expression was assessed on Affymetrix microarrays, and subjected to gene ontology analysis for biological process and cluster-network representation. We found that hypercapnia downregulated the expression of 183 genes and upregulated 126. Among these, major gene clusters linked to immune responses and nucleosome assembly were largely downregulated, while lipid metabolism genes were largely upregulated. The overwhelming majority of these genes were not previously known to be regulated by CO2. These changes in gene expression indicate the potential for hypercapnia to impact bronchial epithelial cell function in ways that may contribute to poor clinical outcomes in patients with severe acute or advanced chronic lung diseases.
2018-09-11 | GSE110362 | GEO
Project description:Hypercapnia, the elevation of CO2 in blood and tissues, commonly occurs in severe acute and chronic respiratory diseases, and is associated with increased risk of mortality. Recent studies have shown that hypercapnia adversely affects innate immunity, host defense, lung edema clearance and cell proliferation. Airway epithelial dysfunction is a feature of advanced lung disease, but the effect of hypercapnia on airway epithelium is unknown. Thus, in the current study we examined the effect of normoxic hypercapnia (20% CO2 for 24 h) vs normocapnia (5% CO2), on global gene expression in differentiated normal human airway epithelial cells. Gene expression was assessed on Affymetrix microarrays, and subjected to gene ontology analysis for biological process and cluster-network representation. We found that hypercapnia downregulated the expression of 183 genes and upregulated 126. Among these, major gene clusters linked to immune responses and nucleosome assembly were largely downregulated, while lipid metabolism genes were largely upregulated. The overwhelming majority of these genes were not previously known to be regulated by CO2. These changes in gene expression indicate the potential for hypercapnia to impact bronchial epithelial cell function in ways that may contribute to poor clinical outcomes in patients with severe acute or advanced chronic lung diseases.
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Project description:In monocytes we used RNA-sequencing to investigate the effect of 4hrs of exposure to buffered hypercapnia (10% CO2) compared to normocapnia (5% CO2) with and without the pro-inflammatory stimulus LPS (2.5ug/ml) for the final 2hrs. Buffered hypercapnia causes transcriptional changes associated with altered metabolic function in both the basal and stimulated states.
2023-04-07 | GSE206333 | GEO
Project description:Hypercapnia has deleterious effects on cell function, including inhibition of alveolar epithelial cells (AEC) and fibroblast proliferation without causing cell death. Classical studies and lineage-trace models demonstrated that fibroblast cells can affect the structurally and functionally distinct alveolar type 1 cells (AT1) and alveolar type 2 cells. This fibroblast cells reprogramming depends on certain signaling pathways that plays critical roles in tissue development and homeostasis throughout the organism lifespan.
2022-12-31 | GSE193538 | GEO
Project description:Skeletal muscle dysfunction and elevated CO2 in the blood, or hypercapnia, are both associated with higher mortality in acute and chronic pulmonary diseases. Hypercapnia causes accelerated protein degradation, reduced protein synthesis, and dysfunctional myogenesis. We have recently reported that hypercapnia-induced skeletal myogenic dysfunction persists after resolution of CO2 exposure, suggesting the existence of durable cellular aberrations in previously hypercapnic cells. No data on lingering myofiber atrophy after hypercapnia resolution currently exist. Hypercapnia and age-induced skeletal muscle loss phenotypically overlap, and myogenic progenitor cells from hypercapnic mice elicit senescence-associated transcriptional programs. While aging is characterized by unique DNA methylation and other epigenetic changes, the potential association of hypercapnia and age-related differential methylation have never been investigated. In the present study, we show that hypercapnic mice elicit protracted muscle deterioration even after returning to normocapnia and demonstrate aberrant DNA methylation in comparison to animals never exposed to elevated CO2. We also show that these DNA methylation changes do not overlap with age-induced alterations.
2025-03-19 | GSE292344 | GEO
Project description:Skeletal muscle dysfunction and elevated CO2 in the blood, or hypercapnia, are both associated with higher mortality in acute and chronic pulmonary diseases. Hypercapnia causes accelerated protein degradation, reduced protein synthesis, and dysfunctional myogenesis. We have recently reported that hypercapnia-induced skeletal myogenic dysfunction persists after resolution of CO2 exposure, suggesting the existence of durable cellular aberrations in previously hypercapnic cells. No data on lingering myofiber atrophy after hypercapnia resolution currently exist. Hypercapnia and age-induced skeletal muscle loss phenotypically overlap, and myogenic progenitor cells from hypercapnic mice elicit senescence-associated transcriptional programs. While aging is characterized by unique DNA methylation and other epigenetic changes, the potential association of hypercapnia and age-related differential methylation have never been investigated. In the present study, we show that hypercapnic mice elicit protracted muscle deterioration even after returning to normocapnia and demonstrate aberrant DNA methylation in comparison to animals never exposed to elevated CO2. We also show that these DNA methylation changes do not overlap with age-induced alterations.
2025-05-20 | GSE297286 | GEO
Project description:Buffered hypercapnia alters the transcriptional profile in monocytes.
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Project description:Hypercapnia alters Wnt production from PDGFR+ lung fibroblasts
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Project description:Chronic CO2 retention, or hypercapnia, occurs in pulmonary diseases and leads to skeletal muscle wasting. Muscle wasting and hypercapnia are independently associated with substantial mortality. While abnormal skeletal muscle stem -satellite- cells, contribute to impaired myogenesis in pulmonary diseases, no mechanistic data exists on hypercapnia-driven dysfunctional satellite cells and myogenesis in-vivo. Autophagy regulates satellite cell activation and myogenesis, and while elevated CO2 inhibits autophagy in inflammatory cells, it has never been evaluated in the context of hypercapnia-driven abnormal myogenesis. Using lineage tracing in pre- and post-stem cell transplantation experiments, we show that hypercapnia undermines both Pax7- and α-7 integrin-expressing satellite cells activation, replication and myogenesis. Satellite cells’ multi-omic analyses indicate that hypercapnia disrupts multiple pathways regulated by autophagy. Moreover, autophagy-specific LC3 fluorescence-reporting mouse and cellular data demonstrate that hypercapnia reduces expressions of AMPK and Ulk1, which critically participate in autophagosome formation, and has no effect on the antagonistic mTOR pathway including Ulk1 serine-757 phosphorylation. Moreover, Atg7 knockout-driven loss of autophagy function phenocopies the effects on hypercapnia. After rapamycin administration, the hypercapnia-induced myogenic deficit is corrected by a sharp AMPK activation leading to the autophagy-stimulatory Ulk1 phosphorylation at serine-555, autophagy acceleration, increased satellite cells replication and improved myogenesis post-satellite cells transplantation.
2025-01-15 | GSE266996 | GEO
Project description:The effects of elevated CO2 (hypercapnia) on organisms are not well known, nor are the molecular pathways by which organisms sense CO2. We have performed microarray analysis on Drosophila in order to develop a genetic model for better understanding the effects of CO2. Equal numbers of 5-day old male and female flies (at least 40 total) were exposed to 13% CO2 or air for 24h and RNA extracted. Gene expression changes in CO2 compared with air were analyzed. Experiments were performed in triplicate and the 3 separate microarray experiments are included.
2010-06-25 | E-GEOD-17444 | biostudies-arrayexpress