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Role of inactive Rhomboid protease 2 (iRhom2) in intestinal ischemia-reperfusion-mediated acute lung injury
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- Authors
- Advisor
- 김주성
- Major
- 의과대학 의학과
- Issue Date
- 2018-08
- Publisher
- 서울대학교 대학원
- Description
- 학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의학과, 2018. 8. 김주성.
- Abstract
- Background/Aim: Intestinal ischemia-reperfusion (I/R) induces distant organ damage, and acute lung injury after intestinal I/R is the most serious complication. However, the detailed mechanism of this inflammatory cascade has not been fully elucidated. Inactive rhomboid protein 2 (iRhom2) was recently identified as an essential molecule for the maturation of tumor necrosis factor (TNF)-α converting enzyme (TACE), which is required for the secretion of TNF-α. The aim of this study was to evaluate the role of iRhom2 in a mouse model of intestinal I/R.
Methods: Intestinal I/R was performed by clamping the superior mesenteric artery for 1 h, followed by 3 h of reperfusion in iRhom2 knockout (KO) and wild-type (WT) mice. Intestines and lungs were assessed for injury by histology. Neutrophil recruitment and cell apoptosis in the lungs were evaluated with myeloperoxidase (MPO) activity assays and caspase 3 activity and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, respectively. The TNF-α and IL-6 levels were measured in the serum and lung homogenates.
Results: Lung injury following intestinal I/R was significantly attenuated in the iRhom2 KO mice compared with the WT mice. After intestinal I/R, the lungs from the iRhom2 KO mice showed significantly low MPO activity and a marked reduction of cell apoptosis associated with a decreased level of active caspase 3 and decreased TUNEL staining compared with the lungs from the WT mice. However, intestinal injury did not significantly differ between the WT and iRhom2 KO mice. The TNF-α levels were elevated in the serum and lungs of the WT mice with intestinal I/R and significantly reduced in the iRhom2 KO mice with intestinal I/R.
Conclusions: iRhom2 may play a critical role in the pathogenesis of acute lung injury after intestinal I/R, which suggests iRhom2 as a novel therapeutic target for acute lung injury after intestinal I/R injury.
- Language
- English
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