Role of noncoding RNAs in liver fibrosis

Abstract

Liver fibrosis is a wound-healing response following chronic liver injury caused by hepatitis virus infection, obesity, or excessive alcohol. It is a dynamic and reversible process characterized by the activation of hepatic stellate cells and excess accumulation of extracellular matrix. Advanced fibrosis could lead to cirrhosis and even liver cancer, which has become a significant health burden worldwide. Many studies have revealed that noncoding RNAs (ncRNAs), including microRNAs, long noncoding RNAs and circular RNAs, are involved in the pathogenesis and development of liver fibrosis by regulating signaling pathways including transforming growth factor-β pathway, phosphatidylinositol 3-kinase/protein kinase B pathway, and Wnt/β-catenin pathway. NcRNAs in serum or exosomes have been reported to tentatively applied in the diagnosis and staging of liver fibrosis and combined with elastography to improve the accuracy of diagnosis. NcRNAs mimics, ncRNAs in mesenchymal stem cell-derived exosomes, and lipid nanoparticles-encapsulated ncRNAs have become promising therapeutic approaches for the treatment of liver fibrosis. In this review, we update the latest knowledge on ncRNAs in the pathogenesis and progression of liver fibrosis, and discuss the potentials and challenges to use these ncRNAs for diagnosis, staging and treatment of liver fibrosis. All these will help us to develop a comprehensive understanding of the role of ncRNAs in liver fibrosis.

Mechanisms of Epigenetic Regulation in the Fibrogenic Activation of Hepatic Stellate Cells in Non-alcoholic Fatty Liver Disease

“…They have a profibrotic effect by regulating genes in various signaling pathways involved in HSCs activation. 63 ncRNAs are a group of transcripts that do not undergo protein translation. They participate in the regulation of gene expression, including chromatin remodeling, transcriptional and post-transcriptional processes, and gene methylation.…”

“…CircRNAs can serve as RNA-binding proteins, miRNA sponges, and participate in the regulation of transcription, translation, and splicing processes. 63 A large number of ncRNAs are found in the liver, exhibiting altered expression profiles in various diseases, including NAFLD. Moreover, the expression patterns of ncRNAs may vary among different morphological forms of NAFLD.…”

“…It is based on the gene-suppressing effect of miRNAs and the sponging action of lncRNAs and circRNAs on miRNAs. 63 For example, treatment with human umbilical cord mesenchymal stem cells inhibited HSCs activation, protected hepatocytes, and improved LF by up-regulating miR-148-5p expression and attenuating the Notch signaling pathway. 152 miR-150, a typical antifibrotic microRNA, suppresses HSCs activation and prevents collagen types I and IV synthesis by activating HSCs via attenuation of the TGF-β signaling pathway.…”

Pathogenesis and clinical features of severe hepatitis E virus infection

“…With a broad impact range, miRNAs are crucial regulators in many physiological processes and pathological conditions. They are involved in liver regeneration, metabolism, fibrosis, inflammation, and carcinogenesis, with contributions to the pathogenesis of diseases such as cirrhosis, ACLF, MASLD/MASH, and liver cancer[ 140 - 143 ].…”

Targeting Interleukin-17 as a Novel Treatment Option for Fibrotic Diseases

“…Probably they act on the most common fibrotic pathway, mediated by TGF-β, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), and Wnt/β-catenin. An example is represented by liver fibrosis, in which the activation and proliferation of hepatic stellate cells were regulated by miRNA or lncRNA that exerted their pro-fibrotic activity precisely by acting on the pathways just reported [ 110 , 111 ]. There is recent evidence that this pro- or anti-fibrotic activity may be mediated by a dysregulation of T helper cells with consequent variability in the release of IL-17.…”