The miR-199

The miR-199 selleck chemicals Dasatinib and miR-200 families have are circumstantially related to liver fibrosis. TGF��-induced factor (TGIF) and SMAD specific E3 ubiquitin protein ligase 2 (SMURF2), both of which play roles in the TGF�� signaling pathway, are candidate targets of miR-199a* and miR-200b, respectively, as determined by the Targetscan algorithm. The expression of miR-199a* was silenced in several proliferating cell lines excluding fibroblasts [21]. Down regulation of miR-199a, miR-199a* and 200a in chronic liver injury tissue was associated with the hepatocarcinogenesis [9]. miR-199a* is also one of the negative regulators of the HCV replication [22]. According to three target search algorithms (Pictar, miRanda, and Targetscan), the miRNAs that may be associated with the liver fibrosis can regulate several fibrosis-related genes (Table S4).

Aberrant expression of these miRNAs may be closely related to the progress of the chronic liver disease. Epithelial-mesenchymal transition (EMT) describes a reversible series of events during which an epithelial cell loses cell-cell contacts and acquires mesenchymal characteristics [23]. Although EMT is not a common event in adults, this process has been implicated in such instances as wound healing and fibrosis. Recent reports showed that the miR-200 family regulated EMT by targeting EMT accelerator ZEB1 and SIP1 [24]. From our observations, overexpression of miR-200a and miR-200b can be connected to the progression of liver fibrosis. The diagnosis and quantification of fibrosis have traditionally relied on liver biopsy, and this is still true at present.

However, there are a number of drawbacks to biopsy, including the invasive nature of the procedure and inter-observer variability. A number of staging systems have been developed to reduce both the inter-observer variability and intra-observer variability, including the METAVIR, the Knodell fibrosis score, and the Scheuer score. However, the reproducibility of hepatic fibrosis and inflammatory activity is not as consistent [25]. In fact, in our study, the degree of fibrosis of the two arbitrary fibrosis groups was classified using the miRNA expression profile with 80% or greater accuracy (data not shown). Thus, miRNA expression can be used for diagnosis of liver fibrosis. In this study we investigated whether common miRNAs in human and mouse could influence the progression of the liver fibrosis.

The signature of miRNAs expression can also serves as a tool for understanding and investigating the mechanism of the onset and progression of liver fibrosis. The miRNA expression profile has the potential to be a novel biomarker of liver fibrosis. Moreover miRNA expression profiling has further applications in novel anti-fibrosis GSK-3 therapy in CH. Materials and Methods Sample preparation 105 liver tissues samples from chronic hepatitis C patients (genotype 1b) were obtained by fine needle biopsy (Table S1).

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