Intestinal Epithelial Chemokine (C-C Motif) Ligand 7 Overexpression Enhances Acetaminophen-Induced Hepatotoxicity in Mice
Open accessAbstract
Acetaminophen (APAP) overdose-induced hepatotoxicity is the leading cause of drug-induced liver injury worldwide. The related injury pathogenesis is mainly focused on the liver. Here, the authors report that gut barrier disruption may also be involved in APAP hepatotoxicity. APAP administration led to gut leakiness and colonic epithelial chemokine (C-C motif) ligand 7 (CCL7) up-regulation. Intestinal epithelial cell (IEC)-specific CCL7 transgenic mice (CCL7 tgIEC mice) showed markedly increased myosin light chain kinase phosphorylation, and elevated gut permeability and bacterial translocation into the liver compared to wild-type mice. Global transcriptome analysis revealed that the expression of hepatic proinflammatory genes was enhanced in CCL7 tgIEC mice compared with wild-type animals. Moreover, CCL7 overexpression in intestinal epithelial cells significantly augmented APAP-induced acute liver injury. These data provide new evidence that dysfunction of CCL7-mediated gut barrier integrity may be an important contributor to APAP-induced hepatotoxicity.
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APAP-induced liver injury causes impairment of intestinal barrier integrity and increased bacterial translocation in mice.
“Recent studies in mice have demonstrated that APAP-induced liver injury causes impairment of intestinal barrier integrity and increased bacterial translocation29–31”
From Multimodal decoding of human liver regeneration (2024) · cites this paper as [30]
Cites
Chu, H., Duan, Y., Yang, L., & Schnabl, B. (2019) · Gut · doi:10.1136/gutjnl-2018-316307 · Cited by 354 · see citing works
Chen, P., Stärkel, P., Turner, J. R., Ho, S. B., & Schnabl, B. (2015) · Hepatology · doi:10.1002/hep.27489 · Cited by 312 · see citing works
Self-citationBacterial translocation and changes in the intestinal microbiome in mouse models of liver disease
Fouts, D. E., Torralba, M., Nelson, K. E., Brenner, D. A., & Schnabl, B. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.01.019 · Cited by 311 · see citing works
Hu, J., Luo, H., Wang, J., Tang, W., Lu, J., Wu, S., Xiong, Z., Yang, G., Chen, Z., Lan, T., et al. (2017) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.122 · Cited by 126 · see citing works
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Multimodal decoding of human liver regeneration
Matchett, K. P., Wilson-Kanamori, J. R., Portman, J. R., Kapourani, C. A., Fercoq, F., May, S., Zajdel, E., Beltran, M., Sutherland, E. F., Mackey, J. B. G., et al. (2024) · Nature · doi:10.1038/s41586-024-07376-2 · Cited by 140 · see citing works
- Authors
- Niu, M., Luo, Z., Gong, S., Win, S., Kaplowitz, N., Jiang, Y., & Chen, P.
- Affiliations
- Southern Medical University (CN)
- University of Southern California (US)
- Zhujiang Hospital (CN)
- Corresponding author
- Jiang, Yong
- Chen, Peng
- Venue
- The American Journal of Pathology
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 190
- Issue
- 1
- Pages
- 57-67
- ISSN
- 0002-9440 (ISSN-L)
- PMC
- PMC6943379
- OpenAlex
- W2979767392
- Cited by
- 26
- References
- 4
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 1 · 2020: 3
- FWCI
- 2.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- American Journal Of Pathology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Natural Science Foundation of China
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- acetaminophen hepatotoxicity, CCL7, intestinal epithelial cells, intestinal barrier integrity, intestinal permeability, bacterial translocation, myosin light chain kinase, drug-induced liver injury, intestinal inflammation, colonic epithelium
- MeSH terms
- Acetaminophen, Animals, Cell Membrane Permeability, Epithelial Cells, Gene Expression Regulation, Intestines, Male, Mice, Inbred C57BL, Mice, Transgenic, Analgesics, Non-Narcotic, Bacterial Translocation, Gene Expression Profiling, Mice, Chemokine CCL7, Chemical and Drug Induced Liver Injury
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