Abstract
To identify long non-coding RNAs (lncRNAs) and their potential roles in hepatic fibrosis in rat liver issues induced by CCl4, lncRNAs and genes were analyzed in fibrotic rat liver tissues by RNA sequencing and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Differentially expressed (DE) lncRNAs (DE-lncRNAs) and genes were subjected to bioinformatics analysis and used to construct a co-expression network. We identified 10 novel DE-lncRNAs that were downregulated during the hepatic fibrosis process. The cis target gene of DE-lncRNA, XLOC118358, was Met, and the cis target gene of the other nine DE-lncRNAs, XLOC004600, XLOC004605, XLOC004610, XLOC004611, XLOC004568, XLOC004580 XLOC004598, XLOC004601, and XLOC004602 was Nox4. The results of construction of a pathway-DEG co-expression network show that lncRNA-Met and lncRNAs-Nox4 were involved in oxidation-reduction processes and PI3K/Akt signaling pathway. Our results identified 10 DE-lncRNAs related to hepatic fibrosis, and the potential roles of DE-lncRNAs and target genes in hepatic fibrosis might provide new therapeutic strategies for hepatic fibrosis.
Highlights
Hepatic fibrosis results from liver tissue repair disorder after injury, and is characterized by pathological and excessive deposition of extracellular matrix (ECM) [1,2,3]
Our study identified several novel long non-coding RNAs (lncRNAs) related to liver fibrosis by comparison to those reported in a set of 5,000 rat liver-expressed lncRNAs described earlier, and which of the fibrosis-related lncRNAs described in the present study corresponds to one of the 5,000 lncRNAs
By analyzing a rat model of hepatic fibrosis induced by exposure to exogenous chemicals, we identified a number of lncRNAs that are related to hepatic fibrosis, suggesting that exposure to environmental chemicals alters the expression of epigenetic regulators, including xenochemicalresponsive lncRNA genes
Summary
Hepatic fibrosis results from liver tissue repair disorder after injury, and is characterized by pathological and excessive deposition of extracellular matrix (ECM) [1,2,3]. Hepatic stellate cells (HSCs) are activated and transformed into myofibroblast-like cells, which secrete a large amount of ECM, including α smooth muscle actin (αSMA) and type I collagen alpha 1 (ColIα1) [4]. Long noncoding RNA (lncRNA) is endogenous RNA with a molecular weight of more than 200 nucleotides. It exists in the cytoplasm or nucleus and lacks an effective open reading frame and protein coding function. Numerous studies have shown that lncRNAs play an important role in the formation and development of liver fibrosis, mainly through transcriptional
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