Regulatory Functions and Mechanisms of Circular RNAs in Hepatic Stellate Cell Activation and Liver Fibrosis

Chronic liver injury induces the activation of hepatic stellate cells (HSCs) into myofibroblasts, which produce excessive amounts of extracellular matrix (ECM), resulting in tissue fibrosis. If the injury persists, these fibrous scars could be permanent and disrupt liver architecture and function. Currently, effective anti-fibrotic therapies are lacking; hence, understanding molecular mechanisms that control HSC activation could hold a key to the development of new treatments. Recently, emerging studies have revealed roles of circular RNAs (circRNAs), a class of non-coding RNAs that was initially assumed to be the result of splicing errors, as new regulators in HSC activation. These circRNAs can modulate the activity of microRNAs (miRNAs) and their interacting protein partners involved in regulating fibrogenic signaling cascades. In this review, we will summarize the current knowledge of this class of non-coding RNAs for their molecular function in HSC activation and liver fibrosis progression.

Automated summary

Chronic liver injury leads to HSC activation and production of excessive ECM, resulting in tissue fibrosis. Understanding the molecular mechanisms that control HSC activation could lead to the development of new anti-fibrotic therapies. Recent studies have identified circRNAs as new regulators in HSC activation, which can modulate miRNA activity involved in fibrogenic signaling cascades.