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Characterization of Growth-Differentiation Factor 15, a Transforming Growth Factor β Superfamily Member Induced following Liver Injury
Open accessAbstract
We have identified a new murine transforming growth factor beta superfamily member, growth-differentiation factor 15 (Gdf15), that is expressed at highest levels in adult liver. As determined by Northern analysis, the expression of Gdf15 in liver was rapidly and dramatically up-regulated following various surgical and chemical treatments that cause acute liver injury and regeneration. In situ hybridization analysis revealed distinct patterns of Gdf15 mRNA localization that appeared to reflect the known patterns of hepatocyte injury in each experimental treatment. In addition, treatment of two hepatocyte-like cell lines with either carbon tetrachloride or heat shock induced Gdf15 mRNA expression, indicating that direct cellular injury can induce Gdf15 expression in the absence of other cell types, such as inflammatory cells. In order to investigate the potential functions of Gdf15, we created Gdf15 null mice by gene targeting. Homozygous null mice were viable and fertile. Despite the dramatic regulation of Gdf15 expression observed in the partial-hepatectomy and carbon tetrachloride injury models, we found no differences in the injury responses between homozygous null mutants and wild-type mice. Our findings suggest either that Gdf15 does not have a regulatory role in liver injury and regeneration or that Gdf15 function within the liver is redundant with that of other signaling molecules.
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“While GDF15 is not highly expressed in the human liver under basal conditions, it is highly expressed in the liver, adipose, and intestine in mice [[204], [205], [206]].”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [204]
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Metadata
- Authors
- Hsiao, E. C., Koniaris, L. G., Zimmers-Koniaris, T., Sebald, S. M., Huynh, T. V., & Lee, S.-J.
- Affiliations
- Department of Molecular Biology and Genetics
- Johns Hopkins University (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2000-05-01
- Volume
- 20
- Issue
- 10
- Pages
- 3742-3751
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC85678
- OpenAlex
- W2111038476
- Cited by
- 302
- References
- 44
- Citations by year
- 2026: 15 · 2025: 18 · 2024: 18 · 2023: 14 · 2022: 24 · 2021: 18 · 2020: 23 · 2019: 14 · 2018: 15 · 2017: 15 · 2016: 12 · 2015: 5 · 2014: 6 · 2013: 11 · 2012: 11
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Johns Hopkins University
- National Institutes of Health
- National Cancer Institute (5 T32 CA09139, T32CA009139)
- National Institute of General Medical Sciences (T32GM007309, 5T32 GM07309)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › GDF15 and Related Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- growth differentiation factor 15, GDF15, TGF-beta superfamily, liver injury, liver regeneration, hepatocyte injury, gene targeting, carbon tetrachloride, partial hepatectomy, heat shock, gene redundancy
- MeSH terms
- Animals, Bile Ducts, Carbon Tetrachloride, Cells, Cultured, Female, Multigene Family, Hepatectomy, Liver, Liver Regeneration, Male, Mice, Inbred C57BL, Mice, Mutant Strains, Molecular Sequence Data, Organ Size, RNA, Messenger, Tissue Distribution, Up-Regulation, Cytokines, In Situ Hybridization, Mice, Growth Differentiation Factor 15
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