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Cited by 19Endoplasmic Reticulum Stress and DiseaseTrauma, Hemostasis, Coagulopathy, ResuscitationCell death mechanisms and regulation

Modulation of the unfolded protein response during hepatocyte and cardiomyocyte apoptosis in trauma/hemorrhagic shock

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Thacker, Stephen A., Robinson, Prema, Abel, Adam, Tweardy, David J.·2013·Scientific Reports
DOI 10.1038/srep01187PMC PMC3561621
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Abstract

Trauma with hemorrhagic shock (T/HS), has been shown to result in liver injury marked by hepatocyte apoptosis and heart failure marked by cardiomyocyte apoptosis, both of which we have shown to be prevented by IL-6 administration at resuscitation, and Stat3 largely mediated this. As specific mediators have not been delineated, we investigated the unfolded protein response (UPR), which, with marked activation, can lead to apoptosis. Prior studies of hepatic and cardiac injury examined limited repertoires of UPR elements, making it difficult to assess the role of the UPR in T/HS. This study describes the first global examination of the UPR transcriptome in the liver and heart following T/HS, demonstrating organ-specific UPR transcriptome changes. The non-canonical UPR chaperone, Hsp70, was most dysregulated following T/HS and may contribute to hepatocyte protection via an IL-6-mediated pathway, identifying a potential new therapeutic strategy to prevent hepatocyte death and organ dysfunction in T/HS.

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Cited by

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Authors
Thacker, S. A., Robinson, P., Abel, A., & Tweardy, D. J.
Affiliations
Baylor College of Medicine (US)
Corresponding author
Tweardy, David J.
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2013-02-01
Volume
3
Issue
1
Pages
1187-1187
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep01187
PMC
PMC3561621
OpenAlex
W2065054849
Cited by
19
References
0
Citations by year
2026: 1 · 2025: 1 · 2023: 2 · 2021: 3 · 2020: 1 · 2018: 4 · 2017: 3 · 2015: 3 · 2014: 1
FWCI
0.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Defense
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01 HL07619)
  • National Institute of Allergy and Infectious Diseases (T32AI055413)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
  • Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
unfolded protein response, trauma-hemorrhagic shock, hepatocyte apoptosis, cardiomyocyte apoptosis, liver injury, heart failure, HSP70, interleukin-6, STAT3, hepatoprotection, organ dysfunction
MeSH terms
Animals, Male, Recombinant Proteins, Resuscitation, Shock, Hemorrhagic, Shock, Traumatic, Interleukin-6, Rats, Sprague-Dawley, Apoptosis, HSP70 Heat-Shock Proteins, Hepatocytes, Myocytes, Cardiac, STAT3 Transcription Factor, HSP40 Heat-Shock Proteins, Rats, Unfolded Protein Response, Transcriptome

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