RRC ID 76906
Author Mizuno T, Nagano F, Ito Y, Tatsukawa H, Shinoda Y, Takeuchi T, Takahashi K, Tsuboi N, Nagamatsu T, Yamada S, Maruyama S, Hitomi K.
Title Novel function of transglutaminase 2 in extracellular histone-induced acute lung injury.
Journal Biochem Biophys Res Commun
Abstract Extracellular histones induce endothelial damage, resulting in lung haemorrhage; however, the underlying mechanism remains unclear. Factor XIII, as a Ca2+-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.
Volume 678
Pages 179-185
Published 2023-10-20
DOI 10.1016/j.bbrc.2023.08.051
PII S0006-291X(23)00997-X
PMID 37643535
MeSH Acute Lung Injury* / chemically induced Animals Endothelial Cells* Fibrin Histones Mice Mice, Inbred C57BL Protein Glutamine gamma Glutamyltransferase 2
IF 2.985
Resource
Human and Animal Cells UV♀2(RCB1994)