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TWEAK/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice.

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Date
2014
Authors
Karaca, Gamze
Swiderska-Syn, Marzena
Xie, Guanhua
Syn, Wing-Kin
Krüger, Leandi
Machado, Mariana Verdelho
Garman, Katherine
Choi, Steve S
Michelotti, Gregory A
Burkly, Linda C
Ochoa, Begoña
Diehl, Anna Mae
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(12 total)
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Abstract
BACKGROUND & AIMS: Pro-inflammatory cytokines are important for liver regeneration after partial hepatectomy (PH). Expression of Fibroblast growth factor-inducible 14 (Fn14), the receptor for TNF-like weak inducer of apoptosis (TWEAK), is induced rapidly after PH and remains elevated throughout the period of peak hepatocyte replication. The role of Fn14 in post-PH liver regeneration is uncertain because Fn14 is expressed by liver progenitors and TWEAK-Fn14 interactions stimulate progenitor growth, but replication of mature hepatocytes is thought to drive liver regeneration after PH. METHODS: To clarify the role of TWEAK-Fn14 after PH, we compared post-PH regenerative responses in wild type (WT) mice, Fn14 knockout (KO) mice, TWEAK KO mice, and WT mice treated with anti-TWEAK antibodies. RESULTS: In WT mice, rare Fn14(+) cells localized with other progenitor markers in peri-portal areas before PH. PH rapidly increased proliferation of Fn14(+) cells; hepatocytic cells that expressed Fn14 and other progenitor markers, such as Lgr5, progressively accumulated from 12-8 h post-PH and then declined to baseline by 96 h. When TWEAK/Fn14 signaling was disrupted, progenitor accumulation, induction of pro-regenerative cytokines, hepatocyte and cholangiocyte proliferation, and over-all survival were inhibited, while post-PH liver damage and bilirubin levels were increased. TWEAK stimulated proliferation and increased Lgr5 expression in cultured liver progenitors, but had no effect on either parameter in cultured primary hepatocytes. CONCLUSIONS: TWEAK-FN14 signaling is necessary for the healthy adult liver to regenerate normally after acute partial hepatectomy.
Type
Journal article
Subject
Animals
Antibodies
Cell Proliferation
Epithelial Cells
Gene Deletion
Hepatectomy
Hepatocytes
Liver
Liver Regeneration
Mice
Mice, Inbred C57BL
Mice, Knockout
Mitogens
Receptors, Tumor Necrosis Factor
Signal Transduction
Tumor Necrosis Factors
Permalink
https://hdl.handle.net/10161/11083
Published Version (Please cite this version)
10.1371/journal.pone.0083987
Publication Info
Karaca, Gamze; Swiderska-Syn, Marzena; Xie, Guanhua; Syn, Wing-Kin; Krüger, Leandi; Machado, Mariana Verdelho; ... Diehl, Anna Mae (2014). TWEAK/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice. PLoS One, 9(1). pp. e83987. 10.1371/journal.pone.0083987. Retrieved from https://hdl.handle.net/10161/11083.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Choi

Steven Sok Choi

Associate Professor of Medicine
Hepatic stellate cell biology; Hepatic Fibrogenesis; Liver regeneration
Diehl

Anna Mae Diehl

Florence McAlister Distinguished Professor of Medicine
Our lab has a long standing interest in liver injury and repair. To learn more about the mechanisms that regulate this process, we study cultured cells, animal models of acute and chronic liver damage and samples from patients with various types of liver disease. Our group also conducts clinical trials in patients with chronic liver disease. We are particularly interested in fatty liver diseases, such as alcoholic fatty liver disease and nonalcoholi
Garman

Katherine Schuver Garman

Associate Professor of Medicine
My research focuses on injury, repair, and cancer development in the gastrointestinal tract. My laboratory performs translational research with the goal of improving health of the gastrointestinal tract. Our work is based in observations from human clinical research. We use databases of esophageal and colon disease to learn more about clinical risk factors for disease. We also use pathology samples of tumors to study the gastrointestinal tract in different states: healthy, inflamed or da

Gregory Alexander Michelotti

Associate Professor in Medicine
The goal of my research is to elucidate mechanisms underlying catecholamine-induced myocardial hypertrophy and identify unique pathways directing adaptive (physiologic) versus maladaptive (pathologic) responses. Stimulation of α1aAR has been shown to mediate myocardial hypertrophy, culminating in both morphological and genetic cellular changes, however it is unknown if α1ARs simply trigger initial hypertrophic events or rather preferentially activate adaptive
This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.
Alphabetical list of authors with Scholars@Duke profiles.
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