Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Alveolar epithelial cells mitigate neutrophilic inflammation in acute lung injury through regulating mitochondrial fatty acid oxidation

ABSTRACT: Alveolar epithelial cells mitigate neutrophilic inflammation in acute lung injury through regulating mitochondrial fatty acid oxidation

PROVIDER: PRJNA930707 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR23318534_1.fastq.gz	Fastqsanger.gz
	SRR23318534_2.fastq.gz	Fastqsanger.gz
	SRR23318535_1.fastq.gz	Fastqsanger.gz
	SRR23318535_2.fastq.gz	Fastqsanger.gz
	SRR23318536_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 68

Similar Datasets

Alveolar epithelial cells mitigate neutrophilic inflammation in acute lung injury through regulating mitochondrial fatty acid oxidation

Project description:Carnitine palmitoyltransferase 1a (CPT1a) is the key regulator of mitochondrial long-chain fatty acid beta-oxidation (LCFAO). However, the functional significance of AT2 cell-specific LCFAO at baseline and during acute lung injury (ALI) is not fully understood. In this study, Murine models of AT2 cell-specific Cpt1a deletion were generated for investigating the role of CPT1a in regulating AT2 cell function and the severity of lipopolysaccharide-induced murine ALI models.

2024-07-05 | GSE224354 | GEO

Alveolar epithelial cells mitigate neutrophilic inflammation in lung injury through regulating mitochondrial fatty acid oxidation.

Project description:Type 2 alveolar epithelial (AT2) cells of the lung are fundamental in regulating alveolar inflammation in response to injury. Impaired mitochondrial long-chain fatty acid β-oxidation (mtLCFAO) in AT2 cells is assumed to aggravate alveolar inflammation in acute lung injury (ALI), yet the importance of mtLCFAO to AT2 cell function needs to be defined. Here we show that expression of carnitine palmitoyltransferase 1a (CPT1a), a mtLCFAO rate limiting enzyme, in AT2 cells is significantly decreased in acute respiratory distress syndrome (ARDS). In mice, Cpt1a deletion in AT2 cells impairs mtLCFAO without reducing ATP production and alters surfactant phospholipid abundance in the alveoli. Impairing mtLCFAO in AT2 cells via deleting either Cpt1a or Acadl (acyl-CoA dehydrogenase long chain) restricts alveolar inflammation in ALI by hindering the production of the neutrophilic chemokine CXCL2 from AT2 cells. This study thus highlights mtLCFAO as immunometabolism to injury in AT2 cells and suggests impaired mtLCFAO in AT2 cells as an anti-inflammatory response in ARDS.

| S-EPMC11341863 | biostudies-literature

Fatty acid oxidation downregulation in alveolar epithelial 2 cells promotes acute lung injury in obesity

Project description:Obesity is associated with increased risk for acute respiratory distress syndrome (ARDS). High fat diet induced obesity was linked to increased lung injury and bronchoalveolar lavage fluid (BALF) free fatty acids in a hyperoxic model of ARDS. In this study, we show significant transcriptional downregulation of fatty acid oxidation (FAO), the mitochondrial process of breaking down fatty acids, in alveolar epithelial type 2 cells (AEC2) of obese compared to lean mice after hyperoxia. AEC2 from obese mice exhibited increased intracellular lipids, more severe mitochondrial bioenergetic failure and reduced ATP production after hyperoxia compared to lean mice. FAO downregulation in AEC2 through a genetic mouse model targeting carnitine palmitoyltransferase 1A (Cpt1aloxp/loxpSftpcCreERT2+/– mice) resulted in further increased BALF fatty acids and lung injury in obese mice. High fat diet was associated with markers of impaired alveolar epithelial regeneration after hyperoxia, which include reduced surfactant AEC2 lineage markers, as well as reduced surfactant related phospholipids in hyperoxic AEC2, and increased BALF surface tension. In a reanalysis of a human molecular single-cell lung atlas of COVID19 ARDS, significant downregulation of the FAO signature in AEC2 compared to controls was observed only in ARDS patients with BMI >30, and not those with BMI <30.

2025-04-18 | GSE264369 | GEO

Fatty acid oxidation downregulation in alveolar epithelial 2 cells promotes acute lung injury in obesity

Project description:Fatty acid oxidation downregulation in alveolar epithelial 2 cells promotes acute lung injury in obesity

| PRJNA1102267 | ENA

Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation

Project description:Repair of airway epithelia requires metabolic rewiring towards fatty acid oxidation

2023-01-31 | GSE218663 | GEO

SHORT CHAIN FATTY ACIDS MITIGATE OSTEOCLAST-MEDIATED ARTHRITIC BONE REMODELLING

Project description:SHORT CHAIN FATTY ACIDS MITIGATE OSTEOCLAST-MEDIATED ARTHRITIC BONE REMODELLING

| PRJNA1006076 | ENA

Reduced fatty acid synthesis and enhanced oxidation promote human definitive endoderm differentiation

Project description:Metabolic remodeling is one of the earliest events that occur during the early differentiation of embryonic stem cells (ESCs), but how these metabolic changes are regulated and participate in the cell differentiation is still largely undissected. Here, we define the fatty acid metabolism as a key player in definitive endoderm (DE) differentiation from human ESCs. During DE differentiation, lipogenesis is decreased while fatty acid β oxidation is enhanced. This dynamic is due to the phosphorylation of lipogenic enzyme acetyl-CoA carboxylase (ACC), which is mediated by AMP-activated protein kinase (AMPK) and inhibits the de novo fatty acid synthesis. More importantly, inhibition of fatty acid synthesis by either its inhibitors or AMPK agonist, significantly promotes the human endoderm differentiation, while blockade of the fatty acid oxidation by genetic manipulation or chemical antagonists impairs the differentiation. The de novo fatty acid synthesis inhibition and fatty acid β oxidation maintaining contribute to the accumulation of cellular acetyl-CoA, which is the essential substrate for protein acetylation. Further study reveals that SMAD3 acetylation and the subsequent subcellular localization exhibit significant change upon interfering fatty acid metabolism. Mechanistically, the accumulation of cellular acetyl-CoA guarantees the acetylation of key transcription factor SMAD3, which further causes the nuclear localization and activation of SMAD signaling pathway to promote DE differentiation. Thus, our current study reveals a fatty acid synthesis/oxidation shift during early differentiation and presents an instructive role of fatty acid metabolism in regulating human early endoderm differentiation.

2023-07-02 | GSE218319 | GEO

Regulation of lung progenitor plasticity and repair by fatty acid oxidation

Project description:Idiopathic pulmonary fibrosis (IPF) is an age-related interstitial lung disease, characterized by inadequate alveolar regeneration and ectopic bronchiolization. While some molecular pathways regulating lung progenitor cells have been described, the role of metabolic pathways in alveolar regeneration is poorly understood. We report that expression of fatty acid oxidation (FAO) genes significantly diminishes in alveolar epithelial cells of IPF lungs by single-cell RNA sequencing and tissue staining. Genetic and pharmacological inhibition in AT2 cells of carnitine palmitoyltransferase 1a (CPT1a), the rate-limiting enzyme of FAO, promoted mitochondrial dysfunction and acquisition of aberrant intermediate states expressing basaloid, and airway secretory cell markers SCGB1A1, and SCGB3A2. Further, mice with deficiency of CPT1a in AT2 cells show enhanced susceptibility to developing lung fibrosis with an accumulation of epithelial cells expressing markers of intermediate cells, airway secretory cells, and senescence. We found that deficiency of CPT1a causes a decrease in SMAD7 protein levels and TGF-β signaling pathway activation. These findings suggest that the mitochondrial FAO metabolic pathway contributes to the regulation of lung progenitor cell repair responses and deficiency of FAO contributes to aberrant lung repair and the development of lung fibrosis.

2025-02-25 | GSE283885 | GEO

Yap regulates fatty acid oxidation in skeletal muscle

Project description:Yap regulates fatty acid oxidation in skeletal muscle

| PRJNA602868 | ENA

Regulation of lung progenitor plasticity and repair by fatty acid oxidation [scRNA-seq]

2025-02-25 | GSE284440 | GEO