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Journal of Orthopaedic Surgery and Research
Published in: Journal of Orthopaedic Surgery and Research 1/2017

Open Access 01-12-2017 | Research article

Anti-high mobility group box-1 (HMGB1) antibody attenuates kidney damage following experimental crush injury and the possible role of the tumor necrosis factor-α and c-Jun N-terminal kinase pathway

Authors: Bin-Fei Zhang, Peng-Fei Wang, Yu-Xuan Cong, Jin-Lai Lei, Hu Wang, Hai Huang, Shuang Han, Yan Zhuang

Published in: Journal of Orthopaedic Surgery and Research | Issue 1/2017

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Abstract

Background

Inflammation plays a crucial role in kidney damage after crush syndrome (CS). Several researchers report that high mobility group box-1 protein (HMGB1) may be the vital trigger in kidney damage, and tumor necrosis factor-α (TNF-α) and c-Jun N-terminal kinase (JNK) are involve in this pathophysiological process, but their biological roles are unclear. This study aimed to explore the relationship between HMGB1, JNK, and TNF-α in kidney damage.

Methods

The crush injury model was established using weight compression. The reliability of the crush injury model was determined by hematoxylin-eosin (HE) staining. Western blot was used to detect the expression of HMGB1, JNK, and TNF-α, and TUNEL was used to mark apoptotic cells in the renal cortex.

Results

The results showed that the highest expression of HMGB1 in muscle was 12 h after CS. JNK and TNF-α increased and peaked at 1 day after CS in kidneys. Western blot analysis revealed that anti-HMGB1 antibody could downregulate the expression of JNK and TNF-α. Anti-TNF-α could downregulate activation of JNK, and SP600125 could downregulate expression of TNF-α in the kidneys. In addition, anti-HMGB1 antibody, anti-TNF-α antibody, and SP600125 could reduce cellular apoptosis in the renal cortex.

Conclusions

It is possible that JNK and TNF-α commonly contribute to kidney damage by assembling a positive feedback cycle after CS, leading to increased apoptosis in the renal cortex. HMGB1 from the muscle may be the trigger.
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Metadata
Title
Anti-high mobility group box-1 (HMGB1) antibody attenuates kidney damage following experimental crush injury and the possible role of the tumor necrosis factor-α and c-Jun N-terminal kinase pathway
Authors
Bin-Fei Zhang
Peng-Fei Wang
Yu-Xuan Cong
Jin-Lai Lei
Hu Wang
Hai Huang
Shuang Han
Yan Zhuang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Orthopaedic Surgery and Research / Issue 1/2017
Electronic ISSN: 1749-799X
DOI
https://doi.org/10.1186/s13018-017-0614-z

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