siRNA- and miRNA-based therapeutics for liver fibrosis

• Published in: Translational research : the journal of laboratory and clinical medicine Vol. 214; pp. 17 - 29
• Main Authors: Zhao, Zhen, Lin, Chien-Yu, Cheng, Kun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2019
• Subjects: Animals; Humans; Liver Cirrhosis - genetics; Liver Cirrhosis - therapy; MicroRNAs - therapeutic use; Models, Biological; RNA, Small Interfering - therapeutic use; Signal Transduction; Gli; PTPRO; HMGB1; 2-APB; α-SMA; NF-κB; UTR; shRNA; UPR; Tβ4; HSC; RT-qPCR; PDK1; Hh; RNAi; TANGO1; MKL1; IL-4; IL-13; ALK3; Hic-5; MMP; Smo; COL6A1; CCl4; COL6A3; PIP3; αCP2; HIF-1a; PIP2; HDAC2; NLRC5; RTK; TβR1; TβR2; IGFIIR; PCBP2; PDGFR; miRNA; TGF-β; TRPM7; PlGF; RISC; DMN; BMP; EGF; VEGF; siRNA; PI3Ks; RAGE; ECM; COL1A1; COL3A1; COL1A2; TNF-α; HSP47; CP-MSCs; PDGF; COL7A1; COL5A2; GRB2; CHB; ATP; ELF; TIMP; FGFR1; CHC
• ISSN: 1931-5244; 1878-1810; 1878-1810
• DOI: 10.1016/j.trsl.2019.07.007

Liver fibrosis is a wound-healing process induced by chronic liver injuries, such as nonalcoholic steatohepatitis, hepatitis, alcohol abuse, and metal poisoning. The accumulation of excessive extracellular matrix (ECM) in the liver is a key characteristic of liver fibrosis. Activated hepatic stellate cells (HSCs) are the major producers of ECM and therefore play irreplaceably important roles during the progression of liver fibrosis. Liver fibrogenesis is highly correlated with the activation of HSCs, which is regulated by numerous profibrotic cytokines. Using RNA interference to downregulate these cytokines in activated HSCs is a promising strategy to reverse liver fibrosis. Meanwhile, microRNAs (miRNAs) have also been exploited for the treatment of liver fibrosis. This review focuses on the current siRNA- and miRNA-based liver fibrosis treatment strategies by targeting activated HSCs in the liver.