MKK3 depletion attenuates intestinal injury after traumatic hemorrhagic shock by restoring mitochondrial function

被引：0

作者：

Li, Lei ^{[1
,2
]}

Zhang, Zhihao ^{[1
]}

Kuai, Xiangyu ^{[1
]}

Deng, Juxin ^{[1
]}

Qiu, Zhaolei ^{[1
,2
]}

Wang, Zhenjie ^{[1
]}

Jiang, Hai ^{[1
,2
]}

机构：

[1] Bengbu Med Univ, Dept Emergency Surg, Affiliated Hosp 1, 287 Chang Huai Rd, Bengbu 233099, Anhui, Peoples R China

[2] Soochow Univ, Suzhou Med Coll, Suzhou 215123, Jiangsu, Peoples R China

来源：

MOLECULAR BIOLOGY REPORTS | 2024年 / 51卷 / 01期

关键词：

MKK3; Intestinal injury; Traumatic hemorrhagic shock; Mitophagy; MITOPHAGY; MEDIATOR;

D O I：

10.1007/s11033-024-09691-3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

BackgroundTraumatic hemorrhagic shock (THS) is a complex pathophysiological process resulting in multiple organ failure. Intestinal barrier dysfunction is one of the mechanisms implicated in multiple organ failure. The present study aimed to explore the regulatory role of mitogen-activated protein kinase kinase 3 (MKK3) in THS-induced intestinal injury and to elucidate its potential mechanism.MethodsRats were subjected to trauma and hemorrhage to establish a THS animal model. MKK3-targeted lentiviral vectors were injected via the tail vein 72 h before modeling. Twelve hours post-modeling, the mean arterial pressure (MAP) and heart rate (HR) were monitored, and histological injury to the intestine was assessed via H&E staining and transmission electron microscopy. Mitochondrial function and mitochondrial reactive oxygen species (ROS) were evaluated. IEC-6 cells were exposed to hypoxia to mimic intestinal injury following THS in vitro.ResultsMKK3 deficiency alleviated intestinal injury and restored mitochondrial function in intestinal tissues from THS-induced rats and hypoxia-treated IEC-6 cells. In addition, MKK3 deficiency promoted Sirt1/PGC-1 alpha-mediated mitochondrial biogenesis and restricted Pink1/Parkin-mediated mitophagy in the injured intestine and IEC-6 cells. Furthermore, the protective effect of MKK3 knockdown against hypoxia-induced mitochondrial damage was strengthened upon simultaneous LC3B/Pink1/Parkin knockdown or weakened upon simultaneous Sirt1 knockdown.ConclusionMKK3 deficiency protected against intestinal injury induced by THS by promoting mitochondrial biogenesis and restricting excessive mitophagy.

引用

页数：10