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Effects of transglutaminase 2 inhibition on ventilator-induced lung injury Suh IB; Yoon DW; Oh WO; Lee EJ; Min KH; Hur GY; Lee SH; Lee SY; Lee SY; Shin C; Shim JJ; In KH; Kang KH; Kim JHJ Korean Med Sci 2014[Apr]; 29 (4): 556-63This study was performed to examine the role of transglutaminase 2 (TG2) in ventilator-induced lung injury (VILI). C57BL/6 mice were divided into six experimental groups: 1) control group; 2) lipopolysaccharide (LPS) group; 3) lung protective ventilation (LPV) group; 4) VILI group; 5) VILI with cystamine, a TG2 inhibitor, pretreatment (Cyst+VILI) group; and 6) LPV with cystamine pretreatment (Cyst+LPV) group. Acute lung injury (ALI) score, TG2 activity and gene expression, inflammatory cytokines, and nuclear factor-kappaB (NF-kappaB) activity were measured. TG2 activity and gene expression were significantly increased in the VILI group (P < 0.05). Cystamine pretreatment significantly decreased TG2 activity and gene expression in the Cyst+VILI group (P < 0.05). Inflammatory cytokines were higher in the VILI group than in the LPS and LPV groups (P < 0.05), and significantly lower in the Cyst+VILI group than the VILI group (P < 0.05). NF-kappaB activity was increased in the VILI group compared with the LPS and LPV groups (P < 0.05), and significantly decreased in the Cyst+VILI group compared to the VILI group (P = 0.029). The ALI score of the Cyst+VILI group was lower than the VILI group, but the difference was not statistically significant (P = 0.105). These results suggest potential roles of TG2 in the pathogenesis of VILI.|Acute Lung Injury/pathology[MESH]|Animals[MESH]|Cystamine/therapeutic use[MESH]|Cytokines/analysis[MESH]|Enzyme Inhibitors/therapeutic use[MESH]|Enzyme-Linked Immunosorbent Assay[MESH]|GTP-Binding Proteins/*antagonists & inhibitors/genetics/metabolism[MESH]|Gene Expression[MESH]|Lipopolysaccharides/toxicity[MESH]|Male[MESH]|Mice[MESH]|Mice, Inbred C57BL[MESH]|NF-kappa B/metabolism[MESH]|Protein Glutamine gamma Glutamyltransferase 2[MESH]|Respiration, Artificial[MESH]|Transglutaminases/*antagonists & inhibitors/genetics/metabolism[MESH]|Ventilator-Induced Lung Injury/*enzymology/pathology/prevention & control[MESH] |
