TWEAK/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice.
Date
2014
Editors
Journal Title
Journal ISSN
Volume Title
Repository Usage Stats
views
downloads
Citation Stats
Attention Stats
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
Department
Description
Provenance
Citation
Permalink
Published Version (Please cite this version)
Publication Info
Karaca, Gamze, Marzena Swiderska-Syn, Guanhua Xie, Wing-Kin Syn, Leandi Krüger, Mariana Verdelho Machado, Katherine Garman, Steve S Choi, et al. (2014). TWEAK/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice. PLoS One, 9(1). p. 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.
Collections
Scholars@Duke
Katherine Schuver Garman
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 damaged, and with cancer.
Steven Sok Choi
Hepatic stellate cell biology; Hepatic Fibrogenesis; Liver regeneration
Anna Mae Diehl
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 nonalcoholic fatty liver disease (NAFLD).
Research by our group has advanced understanding in two main areas: 1) immune system regulation of liver injury and regeneration and 2)the role of fetal morphogens, such as the hedgehog pathway, in regulating fibrotic responses to liver damage. Our basic research programs have been enjoyed continuous NIH support since 1989. We welcome students, post-doctoral fellows and visiting scientists who have interests in this research area to contact us about training opportunities and potential collaborations.
Since 2001 we have also been an active participant in the NIDDK-funded Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), a national consortium comprised of 8 university medical centers selected to generate a national registry for patients with NAFLD and to conduct multicenter treatment trials for this disorder. We are actively recruiting patients for this program, as well as a number of other industry-supported NAFLD studies.
Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.