Integrative proteomic profiling of lung tissues and blood in acute respiratory distress syndrome

Abstract

IntroductionAcute respiratory distress syndrome and acute lung injury (ARDS/ALI) still lack a recognized diagnostic test and pharmacologic treatments that target the underlying pathology.MethodsTo explore the sensitive non-invasive biomarkers associated with pathological changes in the lung of direct ARDS/ALI, we performed an integrative proteomic analysis of lung and blood samples from lipopolysaccharide (LPS)-induced ARDS mice and COVID-19-related ARDS patients. The common differentially expressed proteins (DEPs) were identified based on combined proteomic analysis of serum and lung samples in direct ARDS mice model. The clinical value of the common DEPs was validated in lung and plasma proteomics in cases of COVID-19-related ARDS. ResultsWe identified 368 DEPs in serum and 504 in lung samples from LPS-induced ARDS mice. Gene ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that these DEPs in lung tissues were primarily enriched in pathways, including IL-17 and B cell receptor signaling pathways, and the response to stimuli. In contrast, DEPs in the serum were mostly involved in metabolic pathways and cellular processes. Through network analysis of protein-protein interactions (PPI), we identified diverse clusters of DEPs in the lung and serum samples. We further identified 50 commonly upregulated and 10 commonly downregulated DEPs in the lung and serum samples. Internal validation with a parallel-reacted monitor (PRM) and external validation in the Gene Expression Omnibus (GEO) datasets further showed these confirmed DEPs. We then validated these proteins in the proteomics of patients with ARDS and identified six proteins (HP, LTA4H, S100A9, SAA1, SAA2, and SERPINA3) with good clinical diagnostic and prognostic value. DiscussionThese proteins can be viewed as sensitive and non-invasive biomarkers associated with lung pathological changes in the blood and could potentially serve as targets for the early detection and treatment of direct ARDS especially in hyperinflammatory subphenotype.

Heterogeneity of immune cells and their communications unveiled by transcriptome profiling in acute inflammatory lung injury

“…S100 Calcium Binding Protein A9 (S100a9) usually present as a heterodimer in vivo , mainly released by immune cells, such as neutrophils and macrophages ( 41 ), and is an early-warning protein for inflammation, initiated by Toll-like Receptor 4 (TLR4) in response to LPS stimulation ( 42 ). Blockade of S100a9 in a mouse model of LPS-induced ALI effectively reduced lung injury by inhibiting the Nlrp3 pathway ( 43 ), and S100a9 was identified as having potential diagnostic and prognostic value in a study on ARDS proteomics ( 44 ). However, S100a9 was not only present in the ARDS mouse model in the pulmonary ALI.…”

Proteomic profiling identifies SPP1 associated with rapidly progressive interstitial lung disease in anti-MDA5-positive dermatomyositis

“…As an acute-phase protein, SAA1 plays a role in regulating inflammation and immunity. Previous studies have reported its upregulation in fibrotic sarcoidosis [ 59 ] and COVID-19-related ARDS [ 60 ]. However, further research is needed to elucidate the specific mechanisms by which SAA1 contributes to interstitial lung lesions.…”