Abstract
Emerging evidences have highlighted the crucial role of microRNAs (miRNAs) in the liver cirrhosis, but the relationship between miR-130a-3p and liver cirrhosis is not entirely clear. As we all know, schistosomiasis, as one of the zoonoses, can lead to liver cirrhosis when it advances. In this study, we investigated the biological functions of miR-130a-3p on the liver fibrosis of schistosomiasis in vivo and in vitro. The mice infected with Schistosoma japonicum (S. japonicum) were treated with lentivirus vector (LV)-miR-130a-3p by hydrodynamic injection through the tail vein. Our findings showed significantly decreased expression of miR-130a-3p both in the serum of patients with cirrhosis and in the liver of mice infected with S. japonicum. The results showed that LV-miR-130a-3p could effectively enter into the liver and alleviate liver granulomatous inflammation and collagen deposition. Simultaneously, LV-miR-130a-3p-promoted macrophages presented the Ly6Clo phenotype, concomitant with the decreased expression of the tissue inhibitor of metalloproteinases (TIMP) 1, and increased the expression of matrix metalloproteinase (MMP) 2, which contributed to the dissolution of collagen. Furthermore, overexpression of miR-130a-3p not only inhibited the activation and proliferation of hepatic stellate cells (HSCs) but also induced the apoptosis of HSCs. In addition, we also confirmed that miR-130a-3p enables to bind with mitogen-activated protein kinase (MAPK) 1 and transforming growth factor-beta receptors (TGFBR) 1 and TGFBR2 genes and inhibit the expressions of these genes. Our findings suggested that miR-130a-3p might represent as the potential candidate biomarker and therapeutic target for the prognosis identification and treatment of schistosomiasis liver fibrosis.
Highlights
Schistosomiasis is one of the most serious parasitic diseases worldwide and is raised as a critical public health issue affecting nearly 200 million people in tropical and subtropical regions [1]
To investigate whether there were any differences of miR-130a-3p levels in the liver between mice infected with S. japonicum and non-infected mice, initially, we established the liver fibrosis of schistosomiasis in a murine model (Supplementary Figure 1) and measured the levels of miR-130a-3p in the liver; the results showed that there were significantly decreased levels of miR130a-3p in the liver of mice infected with S. japonicum after 8 weeks as compared to the non-infected liver (Figure 1A)
The results found that the distributions of the green fluorescent protein (GFP) expressed by LV-miR-130a-3p and lentiviral vector-mediated negative control (LV-NC) were mainly located in the liver, suggesting that miR-130a-3p could colonize in the liver via the lentivirus vector through the tail vein injection (Figure 2A)
Summary
Schistosomiasis is one of the most serious parasitic diseases worldwide and is raised as a critical public health issue affecting nearly 200 million people in tropical and subtropical regions [1]. The main pathological characteristic of schistosomiasis is the massive deposition of eggs in the liver and intestine, which causes the release of soluble antigen and leads to granuloma and subsequent liver fibrosis [2, 3]. Liver fibrosis is an important risk factor for the development of cirrhosis, portal hypertension, and hepatocarcinoma (HCC), or even death [4]. Since advanced liver fibrosis is generally regarded to be irreversible, there is no specific and effective antifibrotic program at the moment [5]. The development of an effective therapeutic target is urgent and necessary for the treatment or prevention of further progression of liver fibrosis. A number of studies have implied the emerging roles of gene-based therapies; they might soon expand the therapeutic arsenal for several liver diseases [6]
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