The role of microRNAs in the pathogenesis, grading and treatment of hepatic fibrosis in schistosomiasis

Abstract

Schistosomiasis is a prevalent parasitic disease worldwide. The main pathological changes of hepatosplenic schistosomiasis are hepatic granuloma and fibrosis due to worm eggs. Portal hypertension and ascites induced by hepatic fibrosis are usually the main causes of death in patients with chronic hepatosplenic schistosomiasis. Currently, no effective vaccine exists for preventing schistosome infections. For quite a long time, praziquantel (PZQ) was widely used for the treatment of schistosomiasis and has shown benefit in treating liver fibrosis. However, drug resistance and chemical toxicity from PZQ are being increasingly reported in recent years; therefore, new and effective strategies for treating schistosomiasis-induced hepatic fibrosis are urgently needed. MicroRNA (miRNA), a non-coding RNA, has been proved to be associated with the development of many human diseases, including schistosomiasis. In this review, we present a balanced and comprehensive view of the role of miRNAs in the pathogenesis, grading, and treatment of schistosomiasis-associated hepatic fibrosis. The multiple regulatory roles of miRNAs, such as promoting or inhibiting the development of liver pathology in murine schistosomiasis are also discussed in depth. Additionally, miRNAs may serve as candidate biomarkers for diagnosing liver pathology of schistosomiasis and as novel therapeutic targets for treating schistosomiasis-associated hepatic fibrosis.

Human microRNAs in host–parasite interaction: a review

“…To date, four schistosomal miRNAs have been isolated from extracellular vesicles in sera from Schistosoma infected individuals, such as Bantam, miR-2c-3p, miR-3488, and miR-2a-5p suggesting that can be used both as a diagnostic tool for infection and to monitor treatment effectiveness (Meningher et al 2016 ). More recently, the role of miRNAs in the pathogenesis of hepatic fibrosis in schistosomiasis caused by both S. japonicum and S. mansoni has been reviewed, highlighting their role in the regulation of antifibrosis and profibrosis mechanisms (Chen et al 2019 ). Moreover, the recent advances in characterizing miRNA profiles in extracellular vesicles secreted by Schistosoma species have upstretched the possibility for validating more parasite-derived miRNAs as potential biomarkers for schistosomiasis detection (Cabantous et al 2017 ).…”

Post-genomic progress in helminth parasitology

“…This appeal comes from the fact that as nucleic acids, they: (i) can be detected with exquisite sensitivity and specificity using polymerase chain reaction (PCR); (ii) are systemically distributed and are detectable in blood and other biofluids and (iii) are generally stable because most are encapsulated in extracellular vesicles (Quintana et al ., 2017; Ghalenoei et al ., 2020). Besides being useful for detecting the presence of parasite infection, dysregulation of host miRNA profiles can identify pathology – for example plasma miRNAs can quantify the extent of liver fibrosis caused by schistosomiasis (Chen et al ., 2019). Diagnostics is one sub-field of parasitology that stands to benefit appreciably from the genomic revolution, due to the improvements in sensitivity, specificity and throughput that genomic data and tools could bring to diagnostic tests.…”

Serum proteomic profiling in patients with advanced Schistosoma japonicum-induced hepatic fibrosis

“…Over time and/or with repeated or long-term infection, these granulomas, which develop at the sites of maximal egg accumulation, progress to severe and often irreversible SHF that disrupts hepatic blood flow, in turn obstructs portal venous flow and may lead to potentially life-threatening variceal bleeding [ 7 , 12 – 14 ]. In addition, some data suggest that the granulomatous response and SHF in the liver continue to worsen and subsequently lead to the development of HCC, even after the administration of effective schistosomicides [ 15 – 18 ]. However, in some individuals, the egg-induced granulomatous response does not lead to severe SHF.…”