title: Gap junctional shuttling of miRNA--A novel pathway of intercellular gene regulation and its prospects in clinical application.
abstract: The gap junctional exchange of small molecules between adjacent cells is crucial for maintaining tissue homeostasis and for a large number of cellular processes, including differentiation and proliferation. miRNAs represent a novel class of signalling molecules capable of crossing gap junction (GJ) channels, thereby directly affecting gene expression in the recipient cell. Here, we give an overview about the current knowledge on the biological significance of miRNA shuttling in different cell types (e.g. stem cells, cardiac cells, macrophages), which indicates the GJ-dependent transfer of miRNA as a general mechanism for intercellular gene regulation. Notably, shuttling via GJs is superior to exosome-mediated intercellular transfer regarding specificity and efficiency. We further elucidate this mechanism as a promising approach for miRNA delivery in clinical applications. Using a cell-based gap junctional dependent system, in vivo delivery of therapeutic miRNAs might become more efficient compared to systemic delivery methods. We will discuss the advantages of such a delivery system and the challenges that have to be overcome for its successful application in miRNA therapy.
authors.affiliation: Department of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Schillingallee 69, 18057 Rostock, Germany. Electronic address: heiko.lemcke@uni-rostock.de.
authors.forename: Heiko
authors.initials: H
authors.lastname: Lemcke
authors.affiliation: Department of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Schillingallee 69, 18057 Rostock, Germany. Electronic address: gustav.steinhoff@med.uni-rostock.de.
authors.forename: Gustav
authors.initials: G
authors.lastname: Steinhoff
authors.affiliation: Department of Cardiac Surgery, Reference and Translation Center for Cardiac Stem Cell Therapy (RTC), University of Rostock, Schillingallee 69, 18057 Rostock, Germany. Electronic address: davidrob@med.uni-rostock.de.
authors.forename: Robert
authors.initials: R
authors.lastname: David
mesh_terms: D000818:Animals; D024201:Bystander Effect; D017629:Gap Junctions / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034443:RNA Transport
chemical_list: D035683:MicroRNAs
keywords: Connexin; Gap junction; Intercellular communication; MiRNA therapy; MiRNA transfer