Pathological Changes in Hepatic Sinusoidal Endothelial Cells in Schistosoma japonicum-Infected Mice

Abstract

Schistosomiasis japonica is a zoonotic parasitic disease causing liver fibrosis. Liver sinusoidal endothelial cells (LSECs) exhibit fenestrations, which promote hepatocyte regeneration and reverses the process of liver fibrosis. To investigate the pathological changes of LSECs in schistosomiasis, we established a Schistosomiasis model. The population, phenotype, and secretory function of LSECs were detected by flow cytometry at 20, 28, and 42 days post infection. The changes in LSEC fenestration and basement membrane were observed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Quantitative real-time PCR and Western blotting were used to detect the expression of molecules associated with epithelial–mesenchymal transition (EMT) and fibrosis of LSECs and the liver. The flow cytometry results showed that the total LSEC proportions, differentiated LSEC proportions, and nitric oxide (NO) secretion of LSECs were decreased, and the proportion of dedifferentiated LSECs increased significantly post infection. The electron microscopy results showed that the number of fenestrate was decreased and there was complete basement membrane formation in LSECs following infection. The qPCR and Western blot results showed that EMT, and fibrosis-related indicators of LSECs and the liver changed significantly during the early stages of infection and were aggravated in the middle and late stages. The pathological changes in LSECs may promote EMT and liver fibrosis induced by Schistosoma japonicum infection.

Liver sinusoidal endothelial cell: An important yet often overlooked player in the liver fibrosis

“…Shao et al [ 76 ] reported that BRG1 suppressed eNOS activity and reduced the bioavailability of NO in LSECs by regulating the vascular secretion signaling of LSECs, contributing to the worsening of liver fibrosis. Similarly, Jiang et al [ 77 ] reported that the infection with schistosoma japonicum resulted in decreased differentiation and increased LSEC dedifferentiation, along with reduced NO secretion and enhanced TGF-β secretion. Meanwhile, several chemical and natural compounds have shown great anti-fibrosis effects via modulating the NO signaling.…”