Back to Search
Start Over
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.
- Source :
-
Journal of orthopaedic surgery and research [J Orthop Surg Res] 2017 Jul 12; Vol. 12 (1), pp. 110. Date of Electronic Publication: 2017 Jul 12. - Publication Year :
- 2017
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Animals
Anthracenes
Crush Syndrome mortality
Crush Syndrome pathology
HMGB1 Protein antagonists & inhibitors
In Situ Nick-End Labeling
Kidney metabolism
Male
Mice, Inbred C57BL
Muscle, Skeletal metabolism
Muscle, Skeletal pathology
Crush Syndrome metabolism
HMGB1 Protein metabolism
Kidney pathology
MAP Kinase Signaling System
Tumor Necrosis Factor-alpha metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1749-799X
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of orthopaedic surgery and research
- Publication Type :
- Academic Journal
- Accession number :
- 28701229
- Full Text :
- https://doi.org/10.1186/s13018-017-0614-z