Autonomic Regulation of Liver Regeneration After Partial Hepatectomy in Mice

Ikeda, Osamu; Ozaki, Michitaka; Murata, Soichiro; Matsuo, Ryota; Nakano, Yoritaka; Watanabe, Motonobu; Hisakura, Katsuji; Myronovych, Andriy; Kawasaki, Takuya; Kohno, Keisuke; Ohkohchi, Nobuhiro

doi:10.1016/j.jss.2008.02.059

« Previous Next »Journal of Surgical Research
Volume 152, Issue 2 , Pages 218-223, April 2009

Autonomic Regulation of Liver Regeneration After Partial Hepatectomy in Mice

Osamu Ikeda, M.D.
- Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
Michitaka Ozaki, M.D., Ph.D.
- Department of Molecular Surgery, Hokkaido University School of Medicine, Sapporo, Japan
Soichiro Murata, M.D., Ph.D.
- Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
Ryota Matsuo, M.D., Ph.D.
- Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
Yoritaka Nakano, M.D.
- Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
Motonobu Watanabe, M.D.
- Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
Katsuji Hisakura, M.D.
- Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
Andriy Myronovych, M.D.
- Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
Takuya Kawasaki, M.D.
- Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
Keisuke Kohno, M.D.
- Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
Nobuhiro Ohkohchi, M.D., Ph.D.
- Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan
- To whom correspondence and reprint requests should be addressed at Department of Surgery, Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan

Received 15 November 2007 published online 12 May 2008.

Background/Aims

The autonomic vagus nerve is thought to play an essential role in liver regeneration since hepatic vagotomy delays hepatic DNA synthesis. However, how the parasympathetic vagus nerve is involved in liver regeneration remains obscure. Kupffer cells are located in liver sinusoids adjacent to hepatocytes and might regulate liver regeneration by releasing interleukin-6 (IL-6). The present study examines the role of the vagus nerve and how Kupffer cells are involved in parasympathetic nerve-mediated liver regeneration in mice.

Methods

We performed surgical vagotomy of the hepatic branch and then partial hepatectomy (PH); some mice received acetylcholine (ACh) agonist/antagonist before PH. We then evaluated liver regeneration and signal transducer and activator of transcription-3 (STAT3) activation. We also investigated whether ACh stimulates IL-6 release from Kupffer cells.

Results

Surgical vagotomy impaired liver regeneration. STAT3, which is activated by IL-6 after hepatectomy and plays a pivotal role in liver regeneration, was less activated in vagotomized mice after PH. Post-PH STAT3 activation was recovered by administering vagotomized mice with an ACh agonist. Furthermore, ACh stimulated IL-6 release in Kupffer cells in vitro.

Conclusion

The parasympathetic system (vagus nerve) contributes to liver regeneration after hepatectomy by stimulating IL-6 release from Kupffer cells followed by STAT3 activation in hepatocytes.

Key Words: liver regeneration, vagus nerve, Kupffer cells, IL-6, STAT3, acetylcholine