Curcumin Reorganizes miRNA Expression in a Mouse Model of Liver Fibrosis

Abstract

Asian Pacific J Cancer Prev, 13 (11), [5405][5406][5407][5408] IntroductionLiver is the main organ involved in gluconeogenesis and in production and transportation of fatty acids and cholesterol in which its metabolic disease is prerequisited for cancer. Tissue fibrosis is a major cause of dysfunction in the hepatic systems (Glass et al., 2011). Hepatic fibrosis is influenced by several epigenetic factors that control the wound-healing response. Fibrosis is the excess deposition of extracellular matrix (ECM) components resulted from an imbalance of ECM molecule metabolism (Jiang et al., 2010; Glass et al., 2011) either by an increased synthesis or decreased degradation of ECM components or both. Collagens are synthesized by mesenchymal cells including fibroblasts and have an important role in the development of fibrosis (Jiang et al., 2010). MiRNAs are the smallest, non-coding RNA, plays important roles in post-transcriptional regulation (Borchert et al., 2006). In the nucleus, the miRNA genes are transcribed as primarymiRNA molecules, next processed forming pre-miRNAs (Lee et al., 2004; Borchert et al., 2006), finally transported to the cytoplasm for further processing (Lee et al., 2003; Lund et al., 2004

Interleukin-22 ameliorates liver fibrosis through miR-200a/beta-catenin

“…The miRNA-200 family was reported to be an important one in liver fibrogenesis1920. A recent study showed that miRNA-200a silencing activated HSC through Keap1, while overexpression of miRNA-200a inhibited HSC proliferation8.…”

Antioxidants in liver health

“…Another mechanism of action of curcumin is by interacting with enzymes or genes implicated in liver cirrhosis. Hassan et al [37] proved effect of curcumin by modulating miRNA 199 and 200 that are the main miRNA associated to liver fibrosis. They showed that miRNA 199 and 200 were increased by the administration of CCl4.…”

The role of curcumin in liver diseases

“…In these models, curcumin showed a major role as an inhibitor of HSC activation; it also seems to be able to reduce liver damage, as well as the a-SMA and procollagen expression in the liver, when administered in CCl 4 -induced liver fibrosis models for 4-8 weeks. The recognized mechanism of action in those models included curcumin's ability to target multiple sites, such as platelet-derived growth factor-b receptor (PDGF-bR) [37], matrix metalloproteinases (MMPs) [37,38], tissue growth factor b (TGFb) [39,40], peroxisome proliferator-activated receptors (PPARc) [41], toll-like receptors (TLRs) [42], apoptotic pathway [43,44], inflammatory cytokines [41,42,45,46] and microRNAs [47,48]. Recently, curcumin's capacity to increase cyclic adenosine monophosphate levels, which leads to an increase in the number of mitochondrial DNA duplicates, has been demonstrated [49].…”