Nature, Published online: 25 March 2026; doi:10.1038/s41586-026-10221-3
Intelligent and miniaturized drug delivery devices leveraging advances in biotechnology, artificial intelligence, electronics and materials science enable treatments with increased precision and responsiveness, with applications in cancer, diabetes, cardiovascular disease and other diseases.
Nat Commun. 2026 Mar 20;17(1):2655. doi: 10.1038/s41467-026-70193-w.
ABSTRACT
Pulmonary fibrosis represents a progressive interstitial lung disease marked by excessive extracellular matrix deposition and architectural distortion. Vascular endothelial cells critically contribute to fibrogenesis through paracrine secretion of pro-fibrotic mediators, yet their mechanobiological regulation remains elusive. Using integrated single-cell multi-omics profiling of human pulmonary fibrosis specimens and experimental fibrosis models induced by bleomycin or silica, we identify mechanosensitive Piezo1 upregulation in Endothelial cells as a hallmark of fibrotic progression. Endothelial-specific Piezo1 knockout significantly attenuates Bleomycin-induced fibrotic remodeling in male mice, establishing its pathogenic necessity. Mechanistically, PIEZO1 activation promotes pulmonary fibrosis development via CAPN2-mediated STAT3 phosphorylation, which may regulate the secretion of the pro-fibrotic molecule interleukin-33. These findings suggest that the endothelial PIEZO1-CAPN2-STAT3-IL33 axis is a potential therapeutic target for PF intervention.
PMID:41862476 | PMC:PMC13004862 | DOI:10.1038/s41467-026-70193-w
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