Abstract
BackgroundSevere sepsis, a major health problem worldwide, has become one of the leading causes of death in ICU patients. Further study on the pathogenesis and treatment of acute kidney injury (AKI) is of great significance to reduce high mortality rate of sepsis. In this study, the mechanism by which ubiquitin specific peptidase 10 (USP10) reduces sepsis-induced AKI was investigated. Ligation and perforation of cecum (CLP) was employed to establish C57BL/6 mouse models of sepsis. Hematoxylin-eosin (H&E) staining was performed to detect renal injury. The concentrations of serum creatinine (Cr), urea nitrogen (BUN) and cystatin C (Cys C) were determined using a QuantiChrom™ Urea Assay kit. RT-qPCR and western blot were conducted to assess the USP10 expression level. DHE staining was used to detect reactive oxygen species (ROS) levels. H2O2, MDA and SOD levels were assessed using corresponding colorimetric kits. Western blot was used to examine the expression levels of Bcl-2, Bax, cleaved caspase-3, Sirt6, Nrf2 and HO-1. MTT assay was used to determine cell viability, whereas TUNEL staining and flow cytometry were used to assess cell apoptosis.ResultsIn this study, we found that USP10 was decreased in CLP-induced mouse renal tissues. We identified that USP10 alleviated renal dysfunction induced by CLP. Moreover, USP10 was found to reduce oxidative stress, and abated LPS-induced renal tubular epithelial cell injury and apoptosis. Finally, we discovered that USP10 promoted activation of the NRF2/HO-1 pathway through SIRT6 and attenuated LPS-induced renal tubular epithelial cell injury.ConclusionsThis study found that USP10 activates the NRF2/ARE signaling through SIRT6. USP10 alleviates sepsis-induced renal dysfunction and reduces renal tubular epithelial cell apoptosis and oxidative stress.
Highlights
Severe sepsis, a major health problem worldwide, has become one of the leading causes of death in ICU patients
Low expression of ubiquitin specific peptidase 10 (USP10) induced by cerebral ischemia/reperfusion is associated with brain injury, and increased USP10 expression has a protective effect against cerebral ischemia injury by inhibiting inflammation and apoptosis through blocking TAK1 signal transduction [8]
We examined the expression of USP10 in kidney tissues of sepsisinduced acute kidney injury (AKI) mouse models, and explored the function of USP10 in sepsis-induced renal dysfunction and renal tubular epithelial cells
Summary
A major health problem worldwide, has become one of the leading causes of death in ICU patients. Further study on the pathogenesis and treatment of acute kidney injury (AKI) is of great significance to reduce high mortality rate of sepsis. The mechanism by which ubiquitin specific peptidase 10 (USP10) reduces sepsis-induced AKI was investigated. RT-qPCR and western blot were conducted to assess the USP10 expression level. Severe sepsis and septic shock are major health problems worldwide and have become one of the leading causes of death in ICU patients [1]. Acute kidney injury (AKI) is the most common complication among sepsis due to multiple organ failure [2, 3]. USP10 is expressed in both sepsis and acute respiratory syndrome patients [9]. The role of USP10 in sepsisinduced organ damage is unclear, AKI in particular, which requires further investigation
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