title: Mesenchymal miR-21 regulates branching morphogenesis in murine submandibular gland in vitro.
abstract: Branching morphogenesis in murine submandibular glands (SMG) is regulated by growth factors, extracellular matrix (ECM) and many biological processes through interactions between the epithelium and the mesenchyme. MicroRNAs (miRNAs) are a set of small, non-protein-coding RNAs that regulate gene expression at the post-transcriptional level. We hypothesized that branching morphogenesis is partly regulated by miRNAs. Forty-four miRNAs and novel miRNA candidates were detected in SMG at embryonic day 13 by a cloning method combined with Argonaute-2 immunoprecipitation. MicroRNA21 (miR-21) expression in the mesenchyme was up-regulated and accelerated by epidermal growth factor, which is known to enhance branching morphogenesis in vitro. Down-regulation of miR-21 in the mesenchyme by locked nucleic acids was associated with a decrease in the number of epithelial buds. Relative quantification of candidates for target genes of miR-21 indicated that two messenger RNAs (for Reck and Pdcd4) were down-regulated in the mesenchyme, where miR-21 expression levels were up-regulated. These results suggest that branching morphogenesis is regulated by miR-21 through gene expression related to ECM degradation in the mesenchyme.
authors.affiliation: Department of Pharmacology, Asahi University School of Dentistry, 1851 Hozumi, Mizuho, Gifu 501–0296, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Hayashi
authors.forename: Noriko
authors.initials: N
authors.lastname: Koyama
authors.forename: Yukio
authors.initials: Y
authors.lastname: Azuma
authors.forename: Masanori
authors.initials: M
authors.lastname: Kashimata
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D066298:In Vitro Techniques; D008648:Mesoderm / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D009024:Morphogenesis; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D013363:Submandibular Gland / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
chemical_list: D017931:DNA Primers; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D009841:Oligonucleotides; C477371:locked nucleic acid; D004815:Epidermal Growth Factor