Cited by 302Liver physiology and pathologyGDF15 and Related BiomarkersTGF-β signaling in diseases

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Characterization of Growth-Differentiation Factor 15, a Transforming Growth Factor β Superfamily Member Induced following Liver Injury

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Hsiao, Edward C., Koniaris, Leonidas G., Zimmers-Koniaris, Teresa, Sebald, Suzanne M., Huynh, Thanh V., Lee, Se-Jin·2000·Molecular and Cellular Biology

DOI 10.1128/mcb.20.10.3742-3751.2000PMC PMC85678

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Abstract

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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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)
ORCID: Hsiao, Edward C.
Koniaris, Leonidas G.
Lee, Se-Jin
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
DOI: 10.1128/mcb.20.10.3742-3751.2000
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
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
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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Characterization of Growth-Differentiation Factor 15, a Transforming Growth Factor β Superfamily Member Induced following Liver Injury

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