Transglutaminase 2 gene ablation protects against renal ischemic injury by blocking constant NF-κB activation
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- 作者：Dae-Seok Kim ; Bora Kim ; Hongmin Tahk ; Dong-Hyun Kim ; Eu-Ree Ahn ; Changsun Choi ; Yoon Jeon ; Seo Young Park ; Ho Lee ; Seung Hyun Oh ; Soo-Youl Kim
- 关键词：Transglutaminase 2 ; Transglutaminase 2 knockout mouse ; Unilateral ureteral obstruction ; Ischemia ; Nuclear factor-κ ; B ; Renal injury
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2010
- 出版时间：17 December 2010
- 年：2010
- 卷：403
- 期：3-4
- 页码：479-484
- 全文大小：944 K
文摘
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.