Netrin-1 promotes liver regeneration possibly by facilitating vagal nerve repair after partial hepatectomy in mice

• Published in: Cellular signalling 2022-03, Vol.91, p.110227-110227, Article 110227
• Main Authors: Wang, Zongding, Jiang, Tiemin, Aji, Tuerganaili, Aimulajiang, Kalibixiati, Liu, Yanshi, Lv, Guodong, Wen, Hao
• Format: Article
• Language: English
• Subjects: Animals; Hepatectomy; Liver - metabolism; Liver - surgery; Liver injury; Liver regeneration; Liver Regeneration - physiology; Mice; Mice, Inbred C57BL; Nerve repair; Netrin-1; Netrin-1 - metabolism; Vagal nerve; Vagus Nerve - surgery
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2021.110227

Hepatic regeneration after hepatectomy is a great concern in clinical practice. Recently, the neuronal guidance protein netrin-1 has been reported to enhance regeneration after nerve injury. The goal of this study was to preliminarily investigate whether netrin-1 stimulates vagus nerve regeneration to promote liver regeneration after partial hepatectomy in mice. The expression of netrin-1 in murine remnant livers after partial hepatectomy (PHx) was evaluated in initial studies. C57BL/6 mice that received exogenous netrin-1 after PHx were used to examine liver regeneration. PHx was performed in wild-type mice after adeno-associated virus injection (Ntn1 gene silencing) to detect the impact of endogenous netrin-1. After PHx and hepatic branch vagotomy (HV), the mice were injected with or without netrin-1 to evaluate the effects on hepatic regeneration and vagal nerve recovery. Significant reductions in netrin-1 at the transcript and protein levels in murine liver tissue after hepatectomy were observed. Subsequent studies of netrin-1 administration revealed the promotion of hepatocyte proliferation and specific growth factors contributing to liver repair and a decrease in hepatic-specific injury enzymes. Furthermore, the opposite results were observed in the netrin-1 knockdown group. HV delayed liver regeneration after PHx. However, this retardation was reversed by exogenous netrin-1 supplementation. In addition, the results of nerve growth and vagal nerve repair in the remnant liver suggested that netrin-1 promoted vagal nerve regeneration after hepatectomy. Netrin-1 accelerates liver regeneration after partial hepatectomy in mice, and the potential mechanism is related to the promotion of vagus nerve repair and regeneration. •Netrin-1 is significantly decreased during the early phase of post-hepatectomy in mice.•Netrin-1 accelerates liver regeneration after partial hepatectomy in mice.•The effect of netrin-1 on liver regeneration is mediated by vagal nerve repair.•Netrin-1 contributes to hepatocyte proliferation is mediated possibly by promoting Schwann cells proliferation and migration.