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

Published in The Journal of Cell Biology. 2002, vol. 157, no. 4, p. 657-663
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/pharmacologyAnimalsCell Movement/drug effects/ physiologyCell Size/drug effects/physiologyCells, CulturedCollagen Type I/biosynthesis/drug effectsExtracellular Matrix/drug effects/metabolismFemaleFibroblasts/cytology/drug effects/ metabolismFluorescent Antibody TechniqueGranulation Tissue/cytology/drug effects/ metabolismMuscle, Smooth/metabolismPeptides/ metabolismProtein Structure, TertiaryRNA, Messenger/drug effects/metabolismRatsRats, WistarRecombinant Fusion Proteins/pharmacologyStress, MechanicalTensile Strength/physiologyWound Healing/drug effects/physiology
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PMID: 11994316
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