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May 20, 2026American Journal of Respiratory and Critical Care Medicine

A74-08 Gene Expression Network Analysis Reveals PDIA3-linked UPR-fibrosis Crosstalk Driving Lung Pathophysiology in Influenza-infected Mice

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Why the study?

Viral-fibrotic sequelae are difficult to manage due to limited biomarkers, therapies, and unclear underlying mechanisms, including correlations between post-influenza gene expression, protein interactions, and pathophysiology.

Population

Time-course influenza infection model in mice

Comparison

Inhibition of PDIA3 evaluated against influenza-induced lung fibrosis and pathophysiology

Design

Preclinical animal study with transcriptomic network analysis

Key result

Inhibition of PDIA3 in influenza-infected mice downregulated ~50 transcripts associated with UPR and lung pathophysiological responses, decreasing influenza-induced pathophysiology and lung fibrosis.

Authors

AKA KumarSGS GhandikotaJWJ Walzer

Discussion

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Overview

May identify targets for post-viral fibrosis; leaves open translation to human biomarkers or therapies.

Key Points

  • This investigation aims to elucidate the gene expression networks driving lung pathophysiology in influenza-infected mice, focusing on PDIA3 and UPR.
  • Conducted weighted gene co-expression network analysis (WGCNA) on lung transcriptomic data from an influenza infection model in mice.
  • Identified 26 gene modules, significantly correlating with oxygen saturation and collagen deposition.
  • Performed functional enrichment analysis using ToppGene Suite to assess gene set associations.
  • Identified two gene sets: one positively correlated with infection and fibrosis, with dysregulation confirmed across lung cell types.
  • Inhibition of PDIA3 downregulated ~50 transcripts linked to UPR and lung pathophysiological responses.
  • Reduced secretion of proteins interacting with PDIA3 led to diminished influenza-induced pathophysiology and fibrosis.

Structured PICO

P
Population
time-course influenza infection model in mice
I
Intervention
inhibition of PDIA3
O
Outcome
oxygen saturation (%SpO2) as measured by pulse oximeter readings and collagen deposition as determined by hydroxyproline assaysurrogate

Inhibition of PDIA3 reduces influenza-induced lung pathophysiology and fibrosis in mice by modulating UPR-related gene expression.

Cite This Study

Kumar et al. (2026) studied Influenza infection and lung fibrosis. PDIA3 inhibition was evaluated on Correlation of gene modules with oxygen saturation (%SpO2) and collagen deposition. Inhibition of PDIA3 in influenza-infected mice downregulated ~50 transcripts associated with UPR and lung pathophysiological responses, decreasing influenza-induced pathophysiology and lung fibrosis.

synapsesocial.com/papers/6a0d5122f03e14405aa9d84dhttps://doi.org/10.1093/ajrccm/aamag162.4216
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