title: Inhibition of type I procollagen production by tRNAVal CTE-HSP47 ribozyme.
abstract: BACKGROUND
  Fibrosis characteristically occurs in the advanced stages of chronic inflammatory diseases, occasionally as the primary lesion, and frequently determines the disease prognosis. Fibrotic lesions consist mostly of collagen, and therefore it may be possible to prevent or treat fibrosis by inhibiting collagen production. Of the currently available therapeutic approaches, however, none is sufficiently effective and specific for inhibition of collagen. Heat shock protein 47 (HSP47) is a collagen-specific molecular chaperone that has been reported to play a pivotal role in secretion of procollagen molecules. Therefore, we have tried to suppress its function to inhibit these various types of collagen.
  
  
  METHODS
  We have developed a novel type of ribozyme by ligating a hammerhead sequence to a tRNA(Val) promoter to facilitate displacing the ribozyme from nucleus to cytoplasm and to constitutive transport element, a binding motif of helicase which unwinds mRNA to render the target sequence on the mRNA accessible to the ribozyme.
  
  
  RESULTS
  The ribozyme thus constructed showed strong activity to cleave HSP47 mRNA and suppress the secretion of type I procollagen in the human primary fibroblast.
  
  
  CONCLUSIONS
  We suggest applicability of this ribozyme as a new modality for antifibrosis therapy.
authors.affiliation: The 4th Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Seiya
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Kiminori
authors.initials: K
authors.lastname: Nakamura
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hamada
authors.forename: Katsunori
authors.initials: K
authors.lastname: Sasaki
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.forename: Kageaki
authors.initials: K
authors.lastname: Kuribayashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sato
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Sato
authors.forename: Minoru
authors.initials: M
authors.lastname: Takahashi
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Kogawa
authors.forename: Junji
authors.initials: J
authors.lastname: Kato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Terui
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Takayama
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Kazunari
authors.initials: K
authors.lastname: Taira
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Niitsu
mesh_terms: D016375:Antisense Elements (Genetics) / Q000235:genetics; D001483:Base Sequence; D024042:Collagen Type I / Q000096:biosynthesis* / Q000378:metabolism; D005786:Gene Expression Regulation; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D012313:RNA / Q000235:genetics / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012366:RNA, Transfer, Val / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D020218:Response Elements
chemical_list: D016375:Antisense Elements (Genetics); D024042:Collagen Type I; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D016337:RNA, Catalytic; D012366:RNA, Transfer, Val; D011993:Recombinant Fusion Proteins; C494660:SERPINH1 protein, human; C427204:hammerhead ribozyme; D012313:RNA; D008156:Luciferases