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Fibrosis-related genes are dysregulated in HCV-induced liver disease



Two major pathways exhibited high dysregulation in early liver fibrosis compared with controls or compared with late liver fibrosis – the transforming growth factor beta (TGF-beta)–related pathway genes and Matrix deposition–associated genes, according to an online report in the journal Gene.

The study examined 105 treatment naive HCV genotype 4–infected patients and 16 healthy subjects. The gene-regulation assays were done via PCR arrays on 84 fibrosis-related genes followed by customization of a smaller array consisting of 11 genes that were designed on the bases of results obtained from the larger array. Genes that displayed significant dysregulation at mRNA levels were validated at protein levels, according to the authors.

Hepatitis C Courtesy U.S. Department of Veterans Affairs
Hepatic stellate cell activators (i.e., TGF-beta pathway genes) were considerably overexpressed at transcriptional levels early on in HCV patients compared with controls, whereas expression of their inhibitor TGIF1 was simultaneously downregulated. Extracellular matrix proteins (ECMs) including collagen were upregulated in early fibrosis whereas tissue inhibitors TIMPs 1 and 2 began overexpression in late fibrosis.

The researchers found that the expression at protein levels confirmed the RNA data, thereby excluding dysregulation at posttranscriptional levels.

“We assume that the overall expression pattern of ECM molecules described in the present study may be utilized for a prognostic transcriptomic or proteomic signatures for staging of liver fibrosis,” the authors concluded.

SOURCE: Dawood RM et al. Gene 2018 Apr 21. doi: 10.1016/j.gene.2018.04.032.

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