title: Hepatic Stellate Cells in Liver Fibrosis and siRNA-Based Therapy.
abstract: Hepatic fibrosis is a reversible wound-healing response to either acute or chronic liver injury caused by hepatitis B or C, alcohol, and toxic agents. Hepatic fibrosis is characterized by excessive accumulation and reduced degradation of extracellular matrix (ECM). Excessive accumulation of ECM alters the hepatic architecture leading to liver fibrosis and cirrhosis. Cirrhosis results in failure of common functions of the liver. Hepatic stellate cells (HSC) play a major role in the development of liver fibrosis as HSC are the main source of the excessive production of ECM in an injured liver. RNA interference (RNAi) is a recently discovered therapeutic tool that may provide a solution to manage multiple diseases including liver fibrosis through silencing of specific gene expression in diseased cells. However, gene silencing using small interfering RNA (siRNA) is encountering many challenges in the body after systemic administration. Efficient and stable siRNA delivery to the target cells is a key issue for the development of siRNA therapeutic. For that reason, various viral and non-viral carriers for liver-targeted siRNA delivery have been developed. This review will cover the current strategies for the treatment of liver fibrosis as well as discussing non-viral approaches such as cationic polymers and lipid-based nanoparticles for targeted delivery of siRNA to the liver.
authors.affiliation: College of Pharmacy, Faculty of Health Sciences, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB, Canada, R3E 0T5.
authors.forename: Refaat
authors.initials: R
authors.lastname: Omar
authors.affiliation: College of Pharmacy, Faculty of Health Sciences, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB, Canada, R3E 0T5.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Faculty of Health Sciences, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB, Canada, R3E 0T5.
authors.forename: Haoyuan
authors.initials: H
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Faculty of Health Sciences, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB, Canada, R3E 0T5.|Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, 8613-114 Street, Edmonton, AB, Canada, T6G 2H1.
authors.forename: Neal M
authors.initials: NM
authors.lastname: Davies
authors.affiliation: College of Pharmacy, Faculty of Health Sciences, University of Manitoba, 750 McDermot Avenue, Winnipeg, MB, Canada, R3E 0T5. Yuewen.Gong@ad.umanitoba.ca.
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Gong
mesh_terms: D055166:Hepatic Stellate Cells / Q000473:pathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000473:pathology* / Q000628:therapy; D053758:Nanoparticles / Q000008:administration & dosage; D011108:Polymers / Q000008:administration & dosage; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000627:therapeutic use*
chemical_list: D011108:Polymers; D034741:RNA, Small Interfering
keywords: BMPs; Liver fibrosis; Stellate cells; Targeted delivery; siRNA