Role of iRhom2 in intestinal ischemia-reperfusion-mediated acute lung injury

Scientific Reports
Jee Hyun KimJoo Sung Kim

Abstract

Intestinal ischemia-reperfusion (I/R) may cause acute systemic and lung inflammation. However, the detailed mechanism of this inflammatory cascade has not been fully elucidated. Inactive rhomboid protein 2 (iRhom2) is essential for the maturation of TNF-α converting enzyme (TACE), which is required for TNF-α secretion. We evaluated the role of iRhom2 in a mouse model of intestinal I/R using iRhom2 knockout (KO) and wild-type (WT) mice. Lung injury following intestinal I/R was significantly attenuated in iRhom2 KO mice compared with WT mice. After intestinal I/R, lungs from iRhom2 KO mice showed significantly lower myeloperoxidase (MPO) activity and markedly reduced cell apoptosis associated with a decreased level of active caspase 3 and decreased TUNEL staining compared with lungs from WT mice. TNF-α levels were elevated in the serum and lungs of WT mice with intestinal I/R and significantly reduced in iRhom2 KO mice with intestinal I/R. iRhom2 may play a critical role in the pathogenesis of acute lung injury (ALI) after intestinal I/R and thus may be a novel therapeutic target for ALI after intestinal I/R injury.

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Citations

Mar 21, 2019·Open Biology·Iqbal DullooMatthew Freeman
Oct 6, 2019·Inflammatory Bowel Diseases·Jee Hyun KimJoo Sung Kim
Sep 8, 2020·The FEBS Journal·Colin Adrain, Miguel Cavadas
Dec 10, 2019·Oxidative Medicine and Cellular Longevity·Chaoran ChenGuangli Lu
Sep 12, 2020·International Journal of Molecular Sciences·Mazin A Al-Salihi, Philipp A Lang
Jan 1, 2021·Oxidative Medicine and Cellular Longevity·Marwan AlmoiliqyYuan Lin
Jul 1, 2021·Oxidative Medicine and Cellular Longevity·Guangyao LiZhe Fan

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Methods Mentioned

BETA
PCR
genotyping
enzyme-linked immunosorbent assay
ELISA
SMA

Software Mentioned

GraphPad Prism

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