Proteomics of lung tissue reveals differences in inflammation and alveolar-capillary barrier response between atelectasis and aerated regions

Azman Rashid; Congli Zeng; Gabriel Motta-Ribeiro; Simon T Dillon; Towia A Libermann; Marcos Adriano Lessa; Aranya Bagchi; John Hutchinson; Marcos F Vidal Melo

doi:10.1038/s41598-022-11045-7

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Proteomics of lung tissue reveals differences in inflammation and alveolar-capillary barrier response between atelectasis and aerated regions

Journal article

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Proteomics of lung tissue reveals differences in inflammation and alveolar-capillary barrier response between atelectasis and aerated regions

Azman Rashid, Congli Zeng, Gabriel Motta-Ribeiro, Simon T Dillon, Towia A Libermann, Marcos Adriano Lessa, Aranya Bagchi, John Hutchinson and Marcos F Vidal Melo

Scientific reports, Vol.12(1), 7065

04/29/2022

DOI: 10.1038/s41598-022-11045-7

PMCID: PMC9053128

PMID: 35487970

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Abstract

Atelectasis is a frequent clinical condition, yet knowledge is limited and controversial on its biological contribution towards lung injury. We assessed the regional proteomics of atelectatic versus normally-aerated lung tissue to test the hypothesis that immune and alveolar-capillary barrier functions are compromised by purely atelectasis and dysregulated by additional systemic inflammation (lipopolysaccharide, LPS). Without LPS, 130 proteins were differentially abundant in atelectasis versus aerated lung, mostly (n = 126) with less abundance together with negatively enriched processes in immune, endothelial and epithelial function, and Hippo signaling pathway. Instead, LPS-exposed atelectasis produced 174 differentially abundant proteins, mostly (n = 108) increased including acute lung injury marker RAGE and chemokine CCL5. Functional analysis indicated enhanced leukocyte processes and negatively enriched cell-matrix adhesion and cell junction assembly with LPS. Additionally, extracellular matrix organization and TGF-β signaling were negatively enriched in atelectasis with decreased adhesive glycoprotein THBS1 regardless of LPS. Concordance of a subset of transcriptomics and proteomics revealed overlap of leukocyte-related gene-protein pairs and processes. Together, proteomics of exclusively atelectasis indicates decreased immune response, which converts into an increased response with LPS. Alveolar-capillary barrier function-related proteomics response is down-regulated in atelectasis irrespective of LPS. Specific proteomics signatures suggest biological mechanistic and therapeutic targets for atelectasis-associated lung injury.

Proteomics

Acute Lung Injury - metabolism

Humans

Inflammation - metabolism

Lipopolysaccharides - metabolism

Lung - metabolism

Pulmonary Atelectasis - metabolism

Details

Title: Subtitle: Proteomics of lung tissue reveals differences in inflammation and alveolar-capillary barrier response between atelectasis and aerated regions
Creators: Azman Rashid - Massachusetts General Hospital
Congli Zeng - Columbia University
Gabriel Motta-Ribeiro - Universidade Federal do Rio de Janeiro
Simon T Dillon - Beth Israel Deaconess Medical Center
Towia A Libermann - Beth Israel Deaconess Medical Center
Marcos Adriano Lessa - University of Iowa, Anesthesia
Aranya Bagchi - Massachusetts General Hospital
John Hutchinson - Harvard University
Marcos F Vidal Melo - Columbia University
Resource Type: Journal article
Publication Details: Scientific reports, Vol.12(1), 7065
DOI: 10.1038/s41598-022-11045-7
PMID: 35487970
PMCID: PMC9053128
ISSN: 2045-2322
eISSN: 2045-2322
Grant note: R01 HL121228 / NHLBI NIH HHS R01 HL121228 / NIH HHS
Language: English
Date published: 04/29/2022
Academic Unit: Anesthesia
Record Identifier: 9984656595702771

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