title: Molecular analysis of the TGF-beta controlled gene expression program in chicken embryo dermal myofibroblasts.
abstract: The myofibroblast is a mesenchymal cell characterized by synthesis of the extracellular matrix, plus contractile and secretory activities. Myofibroblasts participate in physiological tissue repair, but can also cause devastating fibrosis. They are present in the tumor stroma of carcinomas and contribute to tumor growth and spreading. As myofibroblasts derive from various cell types and appear in a variety of tissues, there is marked variability in their phenotype. As regulatory mechanisms of wound healing are likely conserved among vertebrates, detailed knowledge of these mechanisms in more distant species will help to distinguish general from specific phenomena. To provide this as yet missing comparison, we analyzed the impact of the chemical inhibition of TGF-beta signaling on gene expression in chicken embryo dermal myofibroblasts. We revealed genes previously reported in mammalian systems (e.g. SPON2, ASPN, COMP, LUM, HAS2, IL6, CXCL12, VEGFA) as well as novel TGF-beta dependent genes, among them PGF, VEGFC, PTN, FAM180A, FIBIN, ZIC1, ADCY2, RET, HHIP and DNER. Inhibition of TGF-beta signaling also induced multiple genes, including NPR3, AGTR2, MTUS1, SOD3 and NOV. We also analyzed the effects of long term inhibition, and found that it is not able to induce myofibroblast dedifferentiation.
authors.affiliation: Laboratory of Molecular Virology, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, CZ-14220 Prague 4, Czech Republic. kosla@img.cas.cz
authors.forename: Jan
authors.initials: J
authors.lastname: Kosla
authors.forename: Michal
authors.initials: M
authors.lastname: Dvorak
authors.forename: Vladimir
authors.initials: V
authors.lastname: Cermak
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics*; D020405:Dermis / Q000187:drug effects / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D058628:Myofibroblasts / Q000187:drug effects / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II