Role of endoplasmic reticulum autophagy in acute lung injury

Liu, Shiping; Fang, Xing; Zhu, Ruiyao; Zhang, Jing; Wang, Huijuan; Lei, Jiaxi; Wang, Chaoqun; Wang, Lu; Zhan, Liying

doi:10.3389/fimmu.2023.1152336

Cited by 2 publications

(1 citation statement)

References 120 publications

(148 reference statements)

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“…Increasing evidence suggests that the pathogenesis of ARDS involves multiple biological functions, including inflammatory response (8), oxidative stress (9), apoptosis (10,11), and endoplasmic reticulum autophagy (12). Amidst these factors, aging is pivotal in the genesis and advancement of ARDS.…”

Section: Introductionmentioning

confidence: 99%

ARDS and aging: TYMS emerges as a promising biomarker and therapeutic target

Li,

Yan,

Zhang

et al. 2024

Front. Immunol.

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BackgroundAcute Respiratory Distress Syndrome (ARDS) is a common condition in the intensive care unit (ICU) with a high mortality rate, yet the diagnosis rate remains low. Recent studies have increasingly highlighted the role of aging in the occurrence and progression of ARDS. This study is committed to investigating the pathogenic mechanisms of cellular and genetic changes in elderly ARDS patients, providing theoretical support for the precise treatment of ARDS.MethodsGene expression profiles for control and ARDS samples were obtained from the Gene Expression Omnibus (GEO) database, while aging-related genes (ARGs) were sourced from the Human Aging Genomic Resources (HAGR) database. Differentially expressed genes (DEGs) were subjected to functional enrichment analysis to understand their roles in ARDS and aging. The Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning pinpointed key modules and marker genes, with ROC curves illustrating their significance. The expression of four ARDS-ARDEGs was validated in lung samples from aged mice with ARDS using qRT-PCR. Gene set enrichment analysis (GSEA) investigated the signaling pathways and immune cell infiltration associated with TYMS expression. Single-nucleus RNA sequencing (snRNA-Seq) explored gene-level differences among cells to investigate intercellular communication during ARDS onset and progression.ResultsARDEGs are involved in cellular responses to DNA damage stimuli, inflammatory reactions, and cellular senescence pathways. The MEmagenta module exhibited a significant correlation with elderly ARDS patients. The LASSO, RRF, and XGBoost algorithms were employed to screen for signature genes, including CKAP2, P2RY14, RBP2, and TYMS. Further validation emphasized the potential role of TYMS in the onset and progression of ARDS. Immune cell infiltration indicated differential proportion and correlations with TYMS expression. SnRNA-Seq and cell-cell communication analysis revealed that TYMS is highly expressed in endothelial cells, and the SEMA3 signaling pathway primarily mediates cell communication between endothelial cells and other cells.ConclusionEndothelial cell damage associated with aging could contribute to ARDS progression by triggering inflammation. TYMS emerges as a promising diagnostic biomarker and potential therapeutic target for ARDS.

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