Abstract
Long non-coding RNAs (lncRNAs) can potentially regulate all aspects of cellular activity including differentiation and development, metabolism, proliferation, apoptosis, and activation, and benefited from advances in transcriptomic and genomic research techniques and database management technologies, its functions and mechanisms in physiological and pathological states have been widely reported. Liver fibrosis is typically characterized by a reversible wound healing response, often accompanied by an excessive accumulation of extracellular matrix. In recent years, a range of lncRNAs have been investigated and found to be involved in several cellular-level regulatory processes as competing endogenous RNAs (ceRNAs) that play an important role in the development of liver fibrosis. A variety of lncRNAs have also been shown to contribute to the altered cell cycle, proliferation profile associated with the accelerated development of liver fibrosis. This review aims to discuss the functions and mechanisms of lncRNAs in the development and regression of liver fibrosis, to explore the major lncRNAs involved in the signaling pathways regulating liver fibrosis, to elucidate the mechanisms mediated by lncRNA dysregulation and to provide new diagnostic and therapeutic strategies for liver fibrosis.
Highlights
1.1 Overview of Liver FibrosisAs a globally important public health problem, liver fibrosis is typically characterized by a reversible wound healing response and an accompanying imbalance between increased synthesis and deposition and decreased degradation of extracellular matrix (ECM), resulting in programmed overaccumulation of ECM components (Nudelman et al, 1998; Aydin and Akcali, 2018)
RNA pull-down analysis suggested that approximately 5% of GAS5 bound to miR-23a compared to 100% of GAS5 in total RNA, and these results suggest that miR-23a could pull down GAS5 in liver tissue and hepatic stellate cells (HSCs). long non-coding RNAs (lncRNAs) GAS5 silencing resulted in increased expression levels of miR-23a while addition of exogenous miR-23a resulted in downregulation of lncRNA GAS5 expression levels, this evidence suggested the lncRNAs in Liver Fibrosis ability of lncRNA GAS5 to bind directly to miR-23a
Research on the involvement of lncRNAs in regulating the development of liver fibrosis are increasing year by year, and the results of in vivo and ex vivo experiments confirm the significant effect of overexpression and knockdown of lncRNAs in reducing or enhancing the extent of liver fibrosis, suggesting that lncRNAs are promising as new targets for liver fibrosis treatment
Summary
As a globally important public health problem, liver fibrosis is typically characterized by a reversible wound healing response and an accompanying imbalance between increased synthesis and deposition and decreased degradation of extracellular matrix (ECM), resulting in programmed overaccumulation of ECM components (Nudelman et al, 1998; Aydin and Akcali, 2018). Numerous epidemiological studies have revealed the etiological role of various chronic liver diseases and associated liver injury-healing reactions in liver fibrosis, such as hepatitis Mechanistic studies at the cellular level suggest that hepatic stellate cells (HSCs) located in the Disse space between hepatic sinusoidal endothelial cells and hepatic epithelial cells and maintaining a close interaction with both are the main sites for the production of ECM components (Geerts, 2001; Khomich et al, 2019), and numerous studies have revealed that their intracellular lipid droplets, which are specific organelles for hepatic retinoic acid storage (Blaner et al, 2009; Elpek, 2014), could lead to liver disease disorders through efflux, depletion, and loss. Studies on the activation mechanisms of hematopoietic stem cells are of great concern in proposing new therapies against hepatic fibrosis and in improving the original strategies (Figure 1)
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