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Single-cell multiomics uncovers an endothelial mechanosensitive PIEZO1-IL-33 axis driving pulmonary fibrosis

GSE314709 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2026/01/30 Platform GPL18573
Summary
Pulmonary fibrosis (PF) represents a progressive interstitial lung disease marked by excessive extracellular matrix deposition and architectural distortion. Vascular endothelial cells (ECs) critically contribute to fibrogenesis through paracrine secretion of pro-fibrotic mediators, yet their mechanobiological regulation remains elusive. UsingThrough integrated single-cell multi-omics profiling of human PF specimens and experimental fibrosis models induced by bleomycin or silica (Bleomycin/SiO2-induced), we identify identified mechanosensitive Piezo1 upregulation in ECs as a hallmark of fibrotic progression. Endothelial-specific Piezo1 knockout significantly attenuates attenuated Bleomycin-induced fibrotic remodeling, establishing its pathogenic necessity. Mechanistically, Piezo1 activation promotes promoted PF development by inducing a pro-fibrotic molecule interleukin-33 (IL-33) secretion via CAPN2-mediated STAT3 phosphorylation. These findings suggest that the endothelial PIEZO1-CAPN2-STAT3-IL-33 axis is a promising therapeutic target for PF intervention.
Published in
Single-cell multiomics uncovers an endothelial mechanosensitive PIEZO1-IL-33 axis driving pulmonary fibrosis
Zhang L, Gui X, Hou R et al. · Nature communications 2026 · PMID 41862476 · doi:10.1038/s41467-026-70193-w
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Also filed as BioProject PRJNA1392477 and SRA study SRP657313. Searching any of these in the dataset finder brings you back here.

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