title: The NH2-terminal peptide of alpha-smooth muscle actin inhibits force generation by the myofibroblast in vitro and in vivo.
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.
authors: Department of Pathology, Centre Médical Universitaire, University of Geneva, 1211 Geneva 4, Switzerland.
authors: Boris
authors: B
authors: Hinz
authors: Giulio
authors: G
authors: Gabbiani
authors: Christine
authors: C
authors: Chaponnier
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006097:Granulation Tissue / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009130:Muscle, Smooth / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D013314:Stress, Mechanical; D013718:Tensile Strength / Q000502:physiology; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology
chemical_list: D000199:Actins; D024042:Collagen Type I; D010455:Peptides; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins