Hydatid cyst fluid promotes peri-cystic fibrosis in cystic echinococcosis by suppressing miR-19 expression.

Chuanshan Zhang,Dominique A Vuitton,Limin Wang,Tuergan Ali,Renyong Lin,Liang Li,Xiaojuan Bi,Junhua Wang,Yingmei Shao,Hao Wen,Guodong Lü

doi:10.1186/s13071-016-1562-x

Abstract

BackgroundEchinococcus granulosus infection causes cystic echinococcosis (CE); the generation of liver fibrosis around the parasitic larval cyst (metacestode) may play a major role in the spontaneous limitation of the parasitic growth; however, fibrogenesis has received little attention in CE. It has been reported that miR-19b plays a role in various diseases, including infectious diseases, by regulating fibrogenesis. However, its function in the development of liver fibrosis in E. granulosus infection is unknown.MethodsThe expression of miR-19b and genes that are involved in liver fibrosis were analysed in E. granulosus-infected human livers using qRT-PCR. The role of miR-19b on hepatic stellate cells (LX-2 cells in vitro) treated with hydatid cyst fluid (HCF) was then analysed by 3-(4, 5-dimet-hylthiazol-2-yl)-2, 4-diphenyl-tetrazolium bromide (MTT) assay, qRT-PCR, Western blot and flow cytometry.ResultsThe results showed that the expression of miR-19 was significantly reduced in the pericystic collagen-rich liver tissue of CE patients, compared to normal liver. Incubation of LX-2 cells (in vitro) with HCF induced a decreased proliferation of these cells and a reduced expression of miR-19, inversely correlated with the expression of collagen 1A1 and TGF-β receptor II (TβRII). Conversely, overexpression of miR-19 by LX-2 cells inhibited the proliferation of these cells and led to decreased TβRII expression.ConclusionsOur study provides new evidence for the intervention of miRNAs in the regulation of fibrosis in infectious diseases; it suggests that E. granulosus can inhibit miR-19 liver expression and promote fibrosis through the increase in TβRII, the activation of hepatic stellate cells and extracellular matrix production.

Highlights

Echinococcus granulosus infection causes cystic echinococcosis (CE); the generation of liver fibrosis around the parasitic larval cyst may play a major role in the spontaneous limitation of the parasitic growth; fibrogenesis has received little attention in CE
Several studies have been published on the characteristics of fibrosis in alveolar echinococcosis (AE), due to E. multilocularis [10]; the role of transforming growth factor β (TGF-β) in host’s tolerance to the metacestode and in the development of fibrosis has been reported in AE [11]
Expression of miR-19b is decreased in patients with CE To assess the progression of liver fibrosis, the expression of fibrosis-related genes was investigated in 39 patients with CE using qRT-PCR; mRNA expression of extracellular matrix (ECM) proteins, COL1A1 and COL3A1 and of α-SMA, were significantly increased

Summary

Introduction

Echinococcus granulosus infection causes cystic echinococcosis (CE); the generation of liver fibrosis around the parasitic larval cyst (metacestode) may play a major role in the spontaneous limitation of the parasitic growth; fibrogenesis has received little attention in CE. Activated HSC can deposit ECM components including collagen (COL) 1A1 and COL3A1, fiA1 and CO and laminin at the site of local tissue damage. They can secrete profibrogenic mediators, such as TGF-β, connective tissue growth factor and platelet-derived growth factor, thereby regulating liver fibrogenesis through a complex feed-back loop [15,16,17]

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