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Regulation of Interstitial Lung Diseases by Pulmonary Endothelial Cells via PLVAP

Zhang, X.; Jia, L.; Hou, R.; Zhao, Y.-a.; Zhang, L.; Tong, X.; Mo, Y.; Zhang, L.

2024-03-12 cell biology
10.1101/2024.03.12.584592 bioRxiv
Show abstract

The lack of standardized treatments for Idiopathic Pulmonary Fibrosis (IPF) and non-IPF progressive fibrotic interstitial lung diseases (non-IPF-PF) highlights the need for identifying common therapeutic targets. We utilize single-cell RNA sequencing data from six disease groups, including IPF and non-IPF-PF such as Sarcoidosis, Systemic Sclerosis (SSc), Non-Specific Interstitial Pneumonitis (NSIP), myositis, and chronic eosinophilic pneumonia (cHP), we conducted subpopulation analysis to identify cells exhibiting a trend of upregulated expression. Pulmonary venous endothelial cells (PVECs) were identified as a significant subpopulation, and targets regulating PVECs upregulation were discerned. In addition, molecular targets are validated through the utilization of in vivo and in vitro methodologies. PVECs showed upregulation in IPF and non-IPF-PF, linked to poorer lung function. PLVAP was consistently elevated across both conditions. In vivo PLVAP knockdown in endothelial cells mitigated pulmonary fibrosis in a bleomycin mouse model, also reducing mesenchymal macrophage interactions. Our findings reveal common therapeutic targets in IPF and non-IPF-PF, offering new directions for treatment strategies.

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