Cited by 59Pancreatitis Pathology and TreatmentAdvanced Glycation End Products researchAcute Kidney Injury Research

Downregulation of HMGB1 protects against the development of acute lung injury after severe acute pancreatitis

Luan, Zheng-Gang, Zhang, Xiao-Juan, Yin, Xiao-Han, Ma, Xiao-Chun, Zhang, Hao, Zhang, Cheng, Guo, Ren-Xuan·2013·Immunobiology

Abstract

Objective To examine the effect of downregulation of high mobility group box 1 (HMGB1) on severe acute pancreatitis (SAP) associated with acute lung injury (ALI), and its subsequent effect on disease severity.Methods Wistar rats were given an IV injection of pRNA-U6.1/Neo-HMGB1, pRNA-U6.1/Neo-vector or saline before induction of SAP. Then, SAP was induced in rats by the retrograde injection of 5% sodium taurocholate into the pancreatic duct. The control group received only a sham operation. Lung and pancreas samples were harvested after induction of SAP. The protein levels of HMGB1, matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1) in lung tissue were investigated. The severity of pancreatic injury was determined by a histological score of pancreatic injury, serum amylase, and pancreatic water content. The lung injury was evaluated by measurement of pulmonary microvascular permeability, lung myeloperoxidase activity and malondialdehyde levels.Results The results found that in pRNA-U6.1/Neo-HMGB1 treated rats, serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were decreased and the severity of pancreatic tissue injury was less compared with either untreated SAP or pRNA-U6.1/Neo-vector treated rats (P<0.05). The administration of pRNA-U6.1/Neo-HMGB1 in SAP-induced rats downregulated the DNA binding activity of the nuclear factor-kappa B (NF-κB) and the expressions of MMP-9 and ICAM-1 in lung. Thus, compared with the untreated SAP rats, the inflammatory response and the severity of ALI decreased (P<0.05).Conclusions These results demonstrate that HMGB1 could augment Inflammation by inducing nuclear translocation of NF-κB, thus aggratating the severity of SAP associated with ALI.

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Crossref · 10.1016/j.imbio.2013.04.013

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  • The downregulation of HMGB1 in hypoxia may signify cytoprotection from cellular damage, such as production of reactive oxygen species, as seen in normoxia cultures.

    “Therefore, its downregulation in hypoxia may signify cytoprotection from cellular damage, such as production of reactive oxygen species, as seen in normoxia cultures [61, 62].”

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Authors
Luan, Z.-G., Zhang, X.-J., Yin, X.-H., Ma, X.-C., Zhang, H., Zhang, C., & Guo, R.-X.
Affiliations
  • First Hospital of China Medical University (CN)
  • General Hospital of Shenyang Military Region (CN)
Venue
Immunobiology
Publisher
Elsevier BV
Published
2013-10
Volume
218
Issue
10
Pages
1261-1270
ISSN
0171-2985 (ISSN-L)
OpenAlex
W2070531069
Cited by
59
References
39
Citations by year
2026: 2 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 5 · 2019: 5 · 2018: 8 · 2017: 5 · 2016: 3 · 2015: 11 · 2014: 3
FWCI
5.58
Type
journal article
Language
en
Open access
closed
Locations
  • Immunobiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
Keywords
HMGB1, severe acute pancreatitis, acute lung injury, RNA interference, NF-κB nuclear translocation, MMP-9, ICAM-1, inflammatory cytokines, TNF-α, IL-1β, lung inflammation, oxidative stress, sodium taurocholate-induced pancreatitis
MeSH terms
Animals, Lung, Male, Protein Binding, Taurocholic Acid, Tumor Necrosis Factor-alpha, Down-Regulation, NF-kappa B, Rats, Wistar, Disease Progression, Intercellular Adhesion Molecule-1, Pancreatitis, Acute Necrotizing, Matrix Metalloproteinase 9, HMGB1 Protein, RNA, Small Interfering, Rats, Interleukin-1beta, Acute Lung Injury

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