title: Cellular or Exosomal microRNAs Associated with CCN Gene Expression in Liver Fibrosis.
abstract: Liver fibrosis occurs during chronic injury and represents, in large part, an exaggerated matrigenic output by hepatic stellate cells (HSCs) which become activated as a result of injury-induced signaling pathways in parenchymal and inflammatory cells (hepatocytes, macrophages, etc.). The molecular components in these pathways (e.g., CCN proteins) are modulated by transcription factors as well as by factors such as microRNAs (miRs) that act posttranscriptionally. MiRs are small (~23 nt) noncoding RNAs that regulate gene expression by specifically interacting with the 3' untranslated region (UTR) of target gene mRNA to repress translation or enhance mRNA cleavage. As well as acting in their cells of production, miRs (and other cellular constituents such as mRNAs and proteins) can be liberated from their cells of origin in nanovesicular membrane exosomes, which traverse the intercellular spaces, and can be delivered to neighboring cells into which they release their molecular payload, causing alterations in gene expression in the target cells. Here we summarize some of the experimental approaches for studying miR action and exosomal trafficking between hepatic cells. Insights into the mechanisms involved will yield new information about how hepatic fibrosis is regulated and, further, may identify new points of therapeutic intervention.
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Research Building 2, 700 Children's Drive, Columbus, OH, 43205, USA. Li.chen@nationwidechildrens.org.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Research Building 2, 700 Children's Drive, Columbus, OH, 43205, USA.|Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, OH, 43212, USA.|Department of Surgery, Wexner Medical Center, The Ohio State University, Columbus, OH, 43212, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Brigstock
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D015415:Biomarkers; D055511:CCN Intercellular Signaling Proteins / Q000235:genetics* / Q000378:metabolism; D002450:Cell Communication; D002458:Cell Fractionation; D018920:Coculture Techniques; D055354:Exosomes / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D055166:Hepatic Stellate Cells / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008103:Liver Cirrhosis / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020413:3' Untranslated Regions; D015415:Biomarkers; D055511:CCN Intercellular Signaling Proteins; D035683:MicroRNAs
keywords: Co-culture; Exosome; Immunohistochemistry; Immunoprecipitation; In situ hybridization; RT-PCR