TARM1 may contribute to acute respiratory distress syndrome progression via regulating M1 macrophage polarization

The underlying pathophysiology of acute respiratory distress syndrome (ARDS), a potentially fatal condition, remains poorly understood. In this work, we screened important genes associated with ARDS and M1 macrophage polarization using publicly available bioinformatics datasets and experimental validation in an attempt to identify potential candidate genes for further investigation in ARDS.

Bulk transcriptomic data from three independent murine ARDS models were analyzed to identify common differentially expressed genes. Single-cell RNA sequencing data from ARDS lungs were used to identify genes differentially expressed between M1 and M2 macrophages. Candidate genes were obtained by intersecting these two gene sets and were validated by qRT-PCR in the lungs of ARDS mice. The top candidate, TARM1, was further investigated in LPS-stimulated RAW264.7 macrophages and in vivo through macrophage-specific AAV6-mediated knockdown.

One important potential gene, TARM1, was markedly elevated in ARDS lung tissue and colocalized with the macrophage marker CD68. TARM1 knockdown in vitro reduced pro-inflammatory cytokine expression and LPS-induced M1 macrophage polarization. In vivo, macrophage-specific TARM1 suppression reduced the lung wet-to-dry ratio, inflammatory cytokine levels, and lung damage.

TARM1 may promote ARDS pathogenesis by regulating macrophage M1 polarization. Macrophage-specific TARM1 inhibition alleviates lung injury, suggesting that TARM1 may be a potential target for further research in ARDS. All transcriptomic and single-cell data analyzed in this study were obtained from public GEO repositories (GSE193958, GSE216943, GSE263867, and GSE217324).