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.
Highlights
Radical or partial hepatectomy is the first line of the therapeutic option for liver diseases, especially for benign and malignant liver tumors [1]
Rozenblum et al [11] demonstrated that the treatment with radiofrequency ablation (RFA) on even a small part of a normal liver can activate the hepatocyte growth factor (HGF)/c-Met kinase pathway and promote vascular endothelial growth factor- (VEGF-) mediated angiogenesis and liver regeneration
To determine the change of liver function after nanosecond pulsed electric field (nsPEF) ablation and the influence of nsPEF ablation on liver regeneration as well as its molecular mechanisms, we investigated the change of serum AST and ALT and weight of ablated mice, followed by the assessment of liver regeneration after nsPEF ablation and the relationship between the liver regeneration and the HGF/c-Met pathway as well as platelet-derived growth factor (PDGF)
Summary
Radical or partial hepatectomy is the first line of the therapeutic option for liver diseases, especially for benign and malignant liver tumors [1]. Rozenblum et al [11] demonstrated that the treatment with RFA on even a small part of a normal liver can activate the hepatocyte growth factor (HGF)/c-Met kinase pathway and promote vascular endothelial growth factor- (VEGF-) mediated angiogenesis and liver regeneration. This depends on the recruitment of activated myofibroblasts or hepatic stellate cells (HSCs), which are responsible for the major production of HGF, to the periablational red zone [10]. To determine the change of liver function after nsPEF ablation and the influence of nsPEF ablation on liver regeneration as well as its molecular mechanisms, we investigated the change of serum AST and ALT and weight of ablated mice, followed by the assessment of liver regeneration after nsPEF ablation and the relationship between the liver regeneration and the HGF/c-Met pathway as well as PDGF
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