RT Journal Article
SR Electronic
T1 TGF-β-R2 is required for HBP induced acute lung injury and vascular leakage for TGF-β/Smad/Rho signaling pathway activation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.01.14.476433
DO 10.1101/2022.01.14.476433
A1 Zixuan Liu
A1 Mingming Chen
A1 Yini Sun
A1 Xu Li
A1 Liu Cao
A1 Xiaochun Ma
YR 2022
UL http://biorxiv.org/content/early/2022/01/16/2022.01.14.476433.abstract
AB Heparin-binding protein (HBP), as a granule protein secreted by polymorphonuclear neutrophils (PMNs) participates in the pathophysiological process of sepsis. It has been reported that HBP is a biomarker of sepsis, which is related to the severity of septic shock and organ dysfunction. HBP binds to vascular endothelial cells as one of the primary target sites. However, it is still unclear whether HBP-binding protein receptors exist on the surface of ECs. The effect of HBP on vascular permeability in sepsis and its mechanism needs to be explored. We conducted in vivo and in vitro study. We demonstrated that HBP bound to transforming growth factor-β receptor type 2 (TGF-β-R2) as a ligand. GST pull-down analysis reveals that HBP mainly interacts with the extracellular domain of TGF-β-R2. HBP induced acute lung injury (ALI) and vascular leakage via activation of TGF-β/SMAD2/3 signaling pathway. Permeability assay suggests TGF-β-R2 is necessary for HBP-induced increased permeability. We also defined the role of HBP and its potential membrane receptor TGF-β-R2 in the blood-gas barrier in the pathogenesis of HBP-related ALI.HBPHeparin-binding proteinTGF-β-R2Transforming growth factor-β receptor type 2EMTEpithelial–mesenchymal transitionHUVECHuman umbilical endothelial cellPMNPolymorphonuclear neutrophilSEMScanning Electron MicroscopeTEMTransmission Electron MicroscopeZOzonula occludensGAPDHglyceraldehyde-3-phosphate dehydrogenaseGSTGlutathione S-transferase.