Pathology and molecular mechanisms of Schistosoma japonicum-associated liver fibrosis

Abstract

Schistosomiasis has been widely disseminated around the world, and poses a significant threat to human health. Schistosoma eggs and soluble egg antigen (SEA) mediated inflammatory responses promote the formation of egg granulomas and liver fibrosis. With continuous liver injuries and inflammatory stimulation, liver fibrosis can develop into liver cirrhosis and liver cancer. Therefore, anti-fibrotic therapy is crucial to increase the survival rate of patients. However, current research on antifibrotic treatments for schistosomiasis requires further exploration. In the complicated microenvironment of schistosome infections, it is important to understand the mechanism and pathology of schistosomiasis-associated liver fibrosis(SSLF). In this review, we discuss the role of SEA in inhibiting liver fibrosis, describe its mechanism, and comprehensively explore the role of host-derived and schistosome-derived microRNAs (miRNAs) in SSLF. Inflammasomes and cytokines are significant factors in promoting SSLF, and we discuss the mechanisms of some critical inflammatory signals and pro-fibrotic cytokines. Natural killer(NK) cells and Natural killer T(NKT) cells can inhibit SSLF but are rarely described, therefore, we highlight their significance. This summarizes and provides insights into the mechanisms of key molecules involved in SSLF development.

Keywords: cytokines; liver fibrosis; molecular mechanisms; schistosomiasis; soluble egg antigen.

Figure 1

The mechanism of SSLF inhibition by Sjp40. Sjp40 inhibited STAT5 activity to promote MicroRNA-155 expression, which down-regulated FOXO3a to inhibit the proliferation and activation of HSCs and upregulation of Let-7b in HSCs to inhibit type I collagen expression. Sjp40 promotes cellular senescence in HSCs by upregulating the SKP2/P27 signaling pathway. Sjp40 promotes Y-Box protein-1 (YB1) expression to initiate BMP-7 transcription. Sjp40 promoted the P53/P21 signaling to inhibit cell proliferation, and P53 promotes nuclear translocation of YB-1. Inhibition of JAK2/STAT3 signaling could inhibit SSLF.

Figure 2

The role of NLRP3 in SSLF. The Dectin-1/Syk signaling pathway promotes NLRP3 inflammasome activation via phosphorylation of ASC. p-syk dependent NOX2 induced production of ROS facilitates NLRP3 inflammasome activation. Vitamin E likely inhibits SSLF by suppressing ROS production and relieving inflammatory injury.