title: Transglutaminase 2 gene ablation protects against renal ischemic injury by blocking constant NF-κB activation.
abstract: Transglutaminase 2 knockout (TGase2(-/-)) mice show significantly reduced inflammation with decreased myofibroblasts in a unilateral ureteral obstruction (UUO) model, but the mechanism remains to be clarified. Nuclear factor-κB (NF-κB) activation plays a major role in the progression of inflammation in an obstructive nephropathy model. However, the key factors extending the duration of NF-κB activation in UUO are not known. In several inflammatory diseases, we and others recently found that TGase 2 plays a key role in extending NF-κB activation, which contributes to the pathogenesis of disease. In the current study, we found that NF-κB activity in mouse embryogenic fibroblasts (MEFs) from TGase2(-/-) mice remained at the control level while the NF-κB activity of wild-type (WT) MEFs was highly increased under hypoxic stress. Using the obstructive nephropathy model, we found that NF-κB activity remained at the control level in TGase2(-/-) mouse kidney tissues, as measured by COX-2 expression, but was highly increased in WT tissues. We conclude that TGase 2 gene ablation reduces the duration of NF-κB activation in ischemic injury.
authors.affiliation: Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute, 111 Jungbalsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 410-769, Republic of Korea.
authors.forename: Dae-Seok
authors.initials: DS
authors.lastname: Kim
authors.forename: Bora
authors.initials: B
authors.lastname: Kim
authors.forename: Hongmin
authors.initials: H
authors.lastname: Tahk
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Eu-Ree
authors.initials: ER
authors.lastname: Ahn
authors.forename: Changsun
authors.initials: C
authors.lastname: Choi
authors.forename: Yoon
authors.initials: Y
authors.lastname: Jeon
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Park
authors.forename: Ho
authors.initials: H
authors.lastname: Lee
authors.forename: Seung Hyun
authors.initials: SH
authors.lastname: Oh
authors.forename: Soo-Youl
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics*; D007511:Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins