title: Hammerhead ribozyme-mediated knockdown of mRNA for fibrotic growth factors: transforming growth factor-beta 1 and connective tissue growth factor.
abstract: Excessive scarring (fibrosis) is a major cause of pathologies in multiple tissues, including lung, liver, kidney, heart, cornea, and skin. The transforming growth factor-β (TGF-β) system has been shown to play a key role in regulating the formation of scar tissue throughout the body. Furthermore, connective tissue growth factor (CTGF) has been shown to mediate most of the fibrotic actions of TGF-β, including stimulation of synthesis of extracellular matrix and differentiation of fibroblasts into myofibroblasts. Currently, no approved drugs selectively and specifically regulate scar formation. Thus, there is a need for a drug that selectively targets the TGF-β cascade at the molecular level and has minimal off-target side effects. This chapter focuses on the design of hammerhead ribozymes, measurement of kinetic activity, and assessment of knockdown mRNAs of TGF-β and CTGF in cell cultures.
authors: Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA.
authors: Paulette M
authors: PM
authors: Robinson
authors: Timothy D
authors: TD
authors: Blalock
authors: Rong
authors: R
authors: Yuan
authors: Alfred S
authors: AS
authors: Lewin
authors: Gregory S
authors: GS
authors: Schultz
mesh_terms: D002454:Cell Differentiation; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005355:Fibrosis / Q000473:pathology; D055785:Gene Knockdown Techniques / Q000379:methods*; D006801:Humans; D016337:RNA, Catalytic / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D016337:RNA, Catalytic; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C427204:hammerhead ribozyme; D055513:Connective Tissue Growth Factor