Author
Listed:
- Tomohito Izumi
(Tohoku University Graduate School of Medicine)
- Junta Imai
(Tohoku University Graduate School of Medicine
PRIME)
- Junpei Yamamoto
(Tohoku University Graduate School of Medicine)
- Yohei Kawana
(Tohoku University Graduate School of Medicine)
- Akira Endo
(Tohoku University Graduate School of Medicine)
- Hiroto Sugawara
(Tohoku University Graduate School of Medicine)
- Masato Kohata
(Tohoku University Graduate School of Medicine)
- Yoichiro Asai
(Tohoku University Graduate School of Medicine)
- Kei Takahashi
(Tohoku University Graduate School of Medicine)
- Shinjiro Kodama
(Tohoku University Graduate School of Medicine)
- Keizo Kaneko
(Tohoku University Graduate School of Medicine)
- Junhong Gao
(Tohoku University Graduate School of Medicine)
- Kenji Uno
(Tohoku University Graduate School of Medicine)
- Shojiro Sawada
(Tohoku University Graduate School of Medicine)
- Vladimir V. Kalinichenko
(Division of Pulmonary Biology, Cincinnati Children’s Hospital Medical Center)
- Yasushi Ishigaki
(Tohoku University Graduate School of Medicine
Iwate Medical University)
- Tetsuya Yamada
(Tohoku University Graduate School of Medicine)
- Hideki Katagiri
(Tohoku University Graduate School of Medicine
Japan Agency for Medical Research and Development, CREST)
Abstract
The liver possesses a high regenerative capacity. Liver regeneration is a compensatory response overcoming disturbances of whole-body homeostasis provoked by organ defects. Here we show that a vagus-macrophage-hepatocyte link regulates acute liver regeneration after liver injury and that this system is critical for promoting survival. Hepatic Foxm1 is rapidly upregulated after partial hepatectomy (PHx). Hepatic branch vagotomy (HV) suppresses this upregulation and hepatocyte proliferation, thereby increasing mortality. In addition, hepatic FoxM1 supplementation in vagotomized mice reverses the suppression of liver regeneration and blocks the increase in post-PHx mortality. Hepatic macrophage depletion suppresses both post-PHx Foxm1 upregulation and remnant liver regeneration, and increases mortality. Hepatic Il-6 rises rapidly after PHx and this is suppressed by HV, muscarinic blockade or resident macrophage depletion. Furthermore, IL-6 neutralization suppresses post-PHx Foxm1 upregulation and remnant liver regeneration. Collectively, vagal signal-mediated IL-6 production in hepatic macrophages upregulates hepatocyte FoxM1, leading to liver regeneration and assures survival.
Suggested Citation
Tomohito Izumi & Junta Imai & Junpei Yamamoto & Yohei Kawana & Akira Endo & Hiroto Sugawara & Masato Kohata & Yoichiro Asai & Kei Takahashi & Shinjiro Kodama & Keizo Kaneko & Junhong Gao & Kenji Uno &, 2018.
"Vagus-macrophage-hepatocyte link promotes post-injury liver regeneration and whole-body survival through hepatic FoxM1 activation,"
Nature Communications, Nature, vol. 9(1), pages 1-13, December.
Handle:
RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07747-0
DOI: 10.1038/s41467-018-07747-0
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