First Author | Mizuno T | Year | 2023 |
Journal | Biochem Biophys Res Commun | Volume | 678 |
Pages | 179-185 | PubMed ID | 37643535 |
Mgi Jnum | J:341155 | Mgi Id | MGI:7532253 |
Doi | 10.1016/j.bbrc.2023.08.051 | Citation | Mizuno T, et al. (2023) Novel function of transglutaminase 2 in extracellular histone-induced acute lung injury. Biochem Biophys Res Commun 678:179-185 |
abstractText | Extracellular histones induce endothelial damage, resulting in lung haemorrhage; however, the underlying mechanism remains unclear. Factor XIII, as a Ca(2+)-dependent cross-linking enzyme in blood, mediates fibrin deposition. As another isozyme, transglutaminase 2 (TG2) has a catalytic activity distributing in most tissues. Herein, we investigated whether TG2 promotes fibrin deposition and mediates the adhesion of platelets to ECs in histone-induced acute lung injury (ALI). We evaluated the lung histology and the adhesion of platelets to endothelial cells (ECs) after injecting histones to wild-type (WT) C57BL/6J and TG2 knockout (TG2(-/-)) mice, and administered a TG2 inhibitor (NC9) to WT mice. Pulmonary haemorrhage was more severe in TG2(-/-) mice than that in WT mice. The area of fibrin deposition and the proportion of CD41(+)CD31(+) cells were lower in TG2(-/-) mice than in WT mice. Pre-treatment of NC9 decreased the area of fibrin deposition and the proportion of CD41(+)CD31(+) cells in WT mice. These results suggest that TG2 prevents from pulmonary haemorrhage in ALI by promoting the adhesion of platelets to ECs and the fibrin deposition. |