dc.contributor.author | Karaca, Gamze | |
dc.contributor.author | Swiderska-Syn, Marzena | |
dc.contributor.author | Xie, Guanhua | |
dc.contributor.author | Syn, Wing-Kin | |
dc.contributor.author | Krueger, Leandi | |
dc.contributor.author | Machado, Mariana Verdelho | |
dc.contributor.author | Garman, Katherine | |
dc.contributor.author | Choi, Steve S. | |
dc.contributor.author | Michelotti, Gregory A. | |
dc.contributor.author | Burkly, Linda C. | |
dc.contributor.author | Ochoa Olascoaga, Begoña | |
dc.contributor.author | Diehl, Anna Mae | |
dc.date.accessioned | 2014-03-28T19:39:55Z | |
dc.date.available | 2014-03-28T19:39:55Z | |
dc.date.issued | 2014-01 | |
dc.identifier.citation | PLoS ONE 9(1) : (2014) // e83987 | es |
dc.identifier.issn | 1932-6203 | |
dc.identifier.uri | http://hdl.handle.net/10810/11875 | |
dc.description.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. | es |
dc.description.sponsorship | Supported by R37 AA010154 and R01 DK077794 | es |
dc.language.iso | eng | es |
dc.publisher | Public Library of Science | es |
dc.rights | info:eu-repo/semantics/openAccess | es |
dc.subject | progenitor cells | es |
dc.subject | stem cells | es |
dc.subject | driven | es |
dc.title | TWEAK/Fn14 Signaling Is Required for Liver Regeneration after Partial Hepatectomy in Mice | es |
dc.type | info:eu-repo/semantics/article | es |
dc.rights.holder | © 2014 Karaca et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | es |
dc.relation.publisherversion | http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0083987 | es |
dc.identifier.doi | 10.1371/journal.pone.0083987 | |
dc.departamentoes | Fisiología | es_ES |
dc.departamentoeu | Fisiologia | es_ES |
dc.subject.categoria | AGRICULTURAL AND BIOLOGICAL SCIENCES | |
dc.subject.categoria | MEDICINE | |
dc.subject.categoria | BIOCHEMISTRY AND MOLECULAR BIOLOGY | |