1. Academic Validation
  2. Upregulation of PDGF Mediates Robust Liver Regeneration after Nanosecond Pulsed Electric Field Ablation by Promoting the HGF/c-Met Pathway

Upregulation of PDGF Mediates Robust Liver Regeneration after Nanosecond Pulsed Electric Field Ablation by Promoting the HGF/c-Met Pathway

  • Biomed Res Int. 2020 Mar 14;2020:3635787. doi: 10.1155/2020/3635787.
Junjie Qian 1 2 3 4 Jianpeng Liu 1 2 3 4 Liangjie Hong 2 3 4 Haohao Lu 2 3 4 Danjing Guo 2 3 4 Zhen Liu 5 Lin Zhou 1 2 3 4 6 Shengyong Yin 1 2 3 4 6 Shusen Zheng 1 2 3 4 6
Affiliations

Affiliations

  • 1 Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
  • 2 NHFPC Key Laboratory of Combined Multi-Organ Transplantation, Hangzhou 310003, China.
  • 3 Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, CAMS, Hangzhou 310003, China.
  • 4 Key Laboratory of Organ Transplantation, Hangzhou, Zhejiang Province 310003, China.
  • 5 Institute of Industrial Ecology and Environment, Zhejiang University, Hangzhou, Zhejiang Province 310007, China.
  • 6 Collaborative Innovation Center for Diagnosis Treatment of Infectious Diseases, China.
Abstract

Nanosecond pulsed electric field (nsPEF) has emerged as a promising tool for hepatocellular carcinoma ablation recently. However, little is known about how nsPEF affects liver regeneration while being applied to eliminate liver lesions. Besides, the impact of nsPEF ablation on liver function should also be taken into consideration in the process. In this paper, we study the impact of nsPEF ablation on liver function by the measurement of serum levels of AST and ALT as well as liver regeneration and relevant molecular mechanisms in vivo. We found that mouse liver function exhibited a temporary injury without weight loss after ablation. In addition, local hepatic nsPEF ablation promoted significant proliferation of hepatocytes of the whole liver with an increase in HGF level. Moreover, the proliferation of hepatocytes was dramatically inhibited by the inhibitor of c-Met. Of interest, the periablational area is characterized by high level of PDGF and a large amount of activated hepatic stellate cells. Furthermore, neutralizing PDGF was able to significantly inhibit liver regeneration, the increased HGF level, and the accumulation of activated HSCs. Our findings demonstrated that nsPEF not only was a safe ablation approach but also could stimulate the regeneration of the whole liver through the activation of the HGF/c-Met pathway by upregulation of PDGF within the periablational zone.

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