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Scientific article
English

The NH2-terminal peptide of alpha-smooth muscle actin inhibits force generation by the myofibroblast in vitro and in vivo

Published inThe Journal of cell biology, vol. 157, no. 4, p. 657-663
Publication date2002
Abstract

Myofibroblasts are specialized fibroblasts responsible for granulation tissue contraction and the soft tissue retractions occurring during fibrocontractive diseases. The marker of fibroblast-myofibroblast modulation is the neo expression of alpha-smooth muscle actin (alpha-SMA), the actin isoform typical of vascular smooth muscle cells that has been suggested to play an important role in myofibroblast force generation. Actin isoforms differ slightly in their NH2-terminal sequences; these conserved differences suggest different functions. When the NH2-terminal sequence of alpha-SMA Ac-EEED is delivered to cultured myofibroblast in the form of a fusion peptide (FP) with a cell penetrating sequence, it inhibits their contractile activity; moreover, upon topical administration in vivo it inhibits the contraction of rat wound granulation tissue. The NH2-terminal peptide of alpha-skeletal actin has no effect on myofibroblasts, whereas the NH2-terminal peptide of beta-cytoplasmic actin abolishes the immunofluorescence staining for this isoform without influencing alpha-SMA distribution and cell contraction. The FPs represent a new tool to better understand the specific functions of actin isoforms. Our findings support the crucial role of alpha-SMA in wound contraction. The alpha-SMA-FP will be useful for the understanding of the mechanisms of connective tissue remodeling; moreover, it furnishes the basis for a cytoskeleton-dependent preventive and/or therapeutic strategy for fibrocontractive pathological situations.

Keywords
  • Actins/genetics/ metabolism/pharmacology
  • Animals
  • Cell Movement/drug effects/ physiology
  • Cell Size/drug effects/physiology
  • Cells, Cultured
  • Collagen Type I/biosynthesis/drug effects
  • Extracellular Matrix/drug effects/metabolism
  • Female
  • Fibroblasts/cytology/drug effects/ metabolism
  • Fluorescent Antibody Technique
  • Granulation Tissue/cytology/drug effects/ metabolism
  • Muscle, Smooth/metabolism
  • Peptides/ metabolism
  • Protein Structure, Tertiary
  • RNA, Messenger/drug effects/metabolism
  • Rats
  • Rats, Wistar
  • Recombinant Fusion Proteins/pharmacology
  • Stress, Mechanical
  • Tensile Strength/physiology
  • Wound Healing/drug effects/physiology
Citation (ISO format)
HINZ, Boris, GABBIANI, Giulio, CHAPONNIER, Christine. The NH2-terminal peptide of alpha-smooth muscle actin inhibits force generation by the myofibroblast in vitro and in vivo. In: The Journal of cell biology, 2002, vol. 157, n° 4, p. 657–663. doi: 10.1083/jcb.200201049
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ISSN of the journal0021-9525
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