The NH2-Terminal Peptide of α-Smooth Muscle Actin Inhibits Force Generation by the Myofibroblast in vitro and in vivo

• Published in: The Journal of cell biology Vol. 157; no. 4; pp. 657 - 663
• Main Authors: Hinz, Boris, Gabbiani, Giulio, Chaponnier, Christine
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 13.05.2002; The Rockefeller University Press
• Subjects: Actins; Actins - genetics; Actins - metabolism; Actins - pharmacology; Animals; Cell Movement - drug effects; Cell Movement - physiology; Cell Size - drug effects; Cell Size - physiology; Cells; Cells, Cultured; Cellular biology; Collagen Type I - biosynthesis; Collagen Type I - drug effects; Collagens; Cultured cells; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Female; Fibroblasts; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - metabolism; Fluorescent Antibody Technique; Granulation tissue; Granulation Tissue - cytology; Granulation Tissue - drug effects; Granulation Tissue - metabolism; Messenger RNA; Muscle, Smooth - metabolism; Muscular system; Myofibroblasts; Peptides; Peptides - metabolism; Protein isoforms; Protein Structure, Tertiary; Rats; Rats, Wistar; Recombinant Fusion Proteins - pharmacology; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Stress fibers; Stress, Mechanical; Tensile Strength - physiology; Washing; Wound Healing - drug effects; Wound Healing - physiology
• DOI: 10.1083/jcb.200201049
• ISSN: 0021-9525

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 α-smooth muscle actin (α-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 α-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 α-skeletal actin has no effect on myofibroblasts, whereas the NH2-terminal peptide of β-cytoplasmic actin abolishes the immunofluorescence staining for this isoform without influencing α-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 α-SMA in wound contraction. The α-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.