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

Publication ,  Journal Article
Karaca, G; Swiderska-Syn, M; Xie, G; Syn, W-K; Krüger, L; Machado, MV; Garman, K; Choi, SS; Michelotti, GA; Burkly, LC; Ochoa, B; Diehl, AM
Published in: PLoS One
2014

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.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

1

Start / End Page

e83987

Location

United States

Related Subject Headings

  • Tumor Necrosis Factors
  • Tumor Necrosis Factor Inhibitors
  • TWEAK Receptor
  • Signal Transduction
  • Receptors, Tumor Necrosis Factor
  • Mitogens
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Liver Regeneration
 

Citation

APA
Chicago
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Karaca, G., Swiderska-Syn, M., Xie, G., Syn, W.-K., Krüger, L., Machado, M. V., … Diehl, A. M. (2014). TWEAK/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice. PLoS One, 9(1), e83987. https://doi.org/10.1371/journal.pone.0083987
Karaca, Gamze, Marzena Swiderska-Syn, Guanhua Xie, Wing-Kin Syn, Leandi Krüger, Mariana Verdelho Machado, Katherine Garman, et al. “TWEAK/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice.PLoS One 9, no. 1 (2014): e83987. https://doi.org/10.1371/journal.pone.0083987.
Karaca G, Swiderska-Syn M, Xie G, Syn W-K, Krüger L, Machado MV, et al. TWEAK/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice. PLoS One. 2014;9(1):e83987.
Karaca, Gamze, et al. “TWEAK/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice.PLoS One, vol. 9, no. 1, 2014, p. e83987. Pubmed, doi:10.1371/journal.pone.0083987.
Karaca G, Swiderska-Syn M, Xie G, Syn W-K, Krüger L, Machado MV, Garman K, Choi SS, Michelotti GA, Burkly LC, Ochoa B, Diehl AM. TWEAK/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice. PLoS One. 2014;9(1):e83987.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2014

Volume

9

Issue

1

Start / End Page

e83987

Location

United States

Related Subject Headings

  • Tumor Necrosis Factors
  • Tumor Necrosis Factor Inhibitors
  • TWEAK Receptor
  • Signal Transduction
  • Receptors, Tumor Necrosis Factor
  • Mitogens
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Liver Regeneration