title: Transforming growth factor-beta1 promotes the morphological and functional differentiation of the myofibroblast.
abstract: The myofibroblast is responsible for the generation of contractile force associated with wound contraction and pathological contractures and is characterized by the presence of alpha-smooth muscle (alpha-sm) actin-containing stress fibers, vinculin-containing fibronexus adhesion complexes, and fibronectin fibrils containing the ED-A splice variant. Transforming growth factor-beta1 (TGF-beta1) can promote the expression of alpha-sm actin in myofibroblasts, but the functional significance of this increased expression is unclear. In this study, we demonstrate, using the stress-relaxed collagen lattice contraction assay, that TGF-beta1 promoted a dose-dependent increase in the generation of contractile force in myofibroblasts and a concomitant increase in the expression of alpha-sm actin. We also demonstrate that TGF-beta1 enhanced the formation of the structural elements important in myofibroblast contractile force generation and transmission, including stress fibers, vinculin-containing fibronexus adhesion complexes, and fibronectin fibrils, and that this enhancement occurred prior to, and independent of, alpha-sm actin expression. This differentiated myofibroblast phenotype was not stable. Removal of TGF-beta1 resulted in reduced expression of alpha-sm actin as well as a decreased assembly of stress fibers and vinculin-containing adhesion complexes; however, there was no reduction in fibronectin fibrils. We conclude that TGF-beta1 promotes the morphological and functional differentiation of the myofibroblast by first enhancing the formation of the structural elements characteristic of the myofibroblast followed by increased expression of alpha-sm actin and contractile force generation.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City 73104, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Vaughan
authors.forename: E W
authors.initials: EW
authors.lastname: Howard
authors.forename: J J
authors.initials: JJ
authors.lastname: Tomasek
mesh_terms: D000199:Actins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*; D014945:Wound Healing
chemical_list: D000199:Actins; D016212:Transforming Growth Factor beta