Current Protein & Peptide ScienceCurrent Protein & Peptide ScienceCurrent Protein & Peptide Science1389-20371875-5550Bentham Science64548810.2174/1389203724666230822085951Life SciencesResearch ArticleUnfolded Protein Response Signaling in Hepatic Stem Cell Activation in Liver FibrosisSalimiZohrehinfo@benthamscience.netRostamiMehdiinfo@benthamscience.netMilasiYaserinfo@benthamscience.netMafiAlirezainfo@benthamscience.netRaoufiniaRamininfo@benthamscience.netKianiAmirhosseininfo@benthamscience.netSakhaeiFaribainfo@benthamscience.netGhezelbashBehroozinfo@benthamscience.netButlerAlexandrainfo@benthamscience.netMohammad-SadeghipourMaryaminfo@benthamscience.netSahebkarAmirhosseininfo@benthamscience.netDepartment of Clinical Biochemistry, School of Pharmacy & Pharmaceutical Sciences, Isfahan University of Medical SciencesDepartment of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical SciencesMedical Genetics and Molecular Medicine Department, School of Medicine, Mashhad University of Medical ScienceDepartment of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical SciencesDepartment of Immunology, School of Medicine, Isfahan University of Medical SciencesResearch Department, Royal College of Surgeons in IrelandDepartment of Clinical Biochemistry, Afzalipoor Faculty of Medicine, Kerman University of Medical SciencesBiotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Science01012024251597011012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://journals.eco-vector.com/1389-2037/article/view/645488

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. Investigating the pathogenic pathways related to the ER/UPR stress axis that contribute to liver fibrosis can help to guide future drug therapy approaches.

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