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

Zongding Wang, Tiemin Jiang, Tuerganaili Aji, Kalibixiati Aimulajiang, Yanshi Liu, Guodong Lv, Hao Wen

Cellular signalling 2022 Mar

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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. Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Zongding Wang, Tiemin Jiang, Tuerganaili Aji, Kalibixiati Aimulajiang, Yanshi Liu, Guodong Lv, Hao Wen. Netrin-1 promotes liver regeneration possibly by facilitating vagal nerve repair after partial hepatectomy in mice. Cellular signalling. 2022 Mar;91:110227