Unfolded Protein Response Signaling in Hepatic Stem Cell Activation in Liver Fibrosis

Frequent exposure to various external and internal adverse forces (stresses) disrupts ‎cell protein homeostasis through endoplasmic reticulum (ER) capacity saturation. ‎This process leads to the unfolded protein response (UPR), which aims to re-establish/maintain ‎optimal cellular equilibrium. This complex mechanism is involved in the pathogenesis of various disorders, such as metabolic syndrome, ‎fibrotic diseases, neurodegeneration, and cancer, by altering cellular metabolic changes integral to ‎activating the hepatic stellate cells (HSCs). The development of hepatic fibrosis is one of ‎the consequences of UPR activation. Therefore, novel therapies that target the UPR pathway effectively and ‎specifically are being studied. This article covers the involvement of the UPR signaling pathway in cellular damage in liver fibrosis and emphasizes the potential role of non-coding RNAs (ncRNA) in this process. Investigating the pathogenic pathways related to the ER/UPR stress axis that contribute to liver fibrosis can help to guide future drug therapy approaches.