Transforming growth factor-beta 1 specifically induce proteins involved in the myofibroblast contractile apparatus

Research output: Contribution to journalArticle

Abstract

Transforming growth factor-beta(1) (TGF-beta(1)) induces alpha-smooth muscle actin (alpha-SMA) and collagen synthesis in fibroblast both in vivo and in vitro and plays a significant role in tissue repair and the development of fibrosis. During these processes the fibroblasts differentiate into activated fibroblasts (so called myofibroblasts), characterized by increased alpha-SMA expression. Because TGF-beta(1) is considered the main inducer of the myofibroblast phenotype and cytoskeletal changes accompany this differentiation, the main objective of this investigation was to study how TGF-beta(1) alters protein expression of cytoskeletal-associated proteins. Metabolic labeling of cell cultures by [(35)S]methionine, followed by protein separation on two-dimensional gel electrophoresis, displayed approximately 2500 proteins in the pI interval of 3-10. Treatment of TGF-beta(1) led to specific spot pattern changes that were identified by mass spectrometry and represent specific induction of several members of the contractile apparatus such as calgizzarin, cofilin, and profilin. These proteins have not previously been shown to be regulated by TGF-beta(1), and the functional role of these proteins is to participate in the depolymerization and stabilization of the microfilaments. These results show that TGF-beta(1) induces not only alpha-SMA but a whole set of actin-associated proteins that may contribute to the increased contractile properties of the myofibroblast. These proteins accompany the induced expression of alpha-SMA and may participate in the formation of stress fibers, cell contractility, and cell spreading characterizing the myofibroblasts phenotype.

Details

Authors
Organisations
External organisations
  • AstraZeneca, Sweden
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Clinical Medicine

Keywords

  • Actin Cytoskeleton, Actin Depolymerizing Factors, Actins, Cell Differentiation, Cells, Cultured, Contractile Proteins, Electrophoresis, Gel, Two-Dimensional, Fibroblasts, Humans, Isotopes, Mass Spectrometry, Microfilament Proteins, Muscle, Smooth, Profilins, S100 Proteins, Transforming Growth Factor beta, Transforming Growth Factor beta1, Journal Article
Original languageEnglish
Pages (from-to)466-477
Number of pages12
JournalMolecular & Cellular Proteomics
Volume3
Issue number5
Publication statusPublished - 2004 May
Publication categoryResearch
Peer-reviewedYes