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This Article Full Text Full Text (PDF) All Versions of this Article: 293/5/C1636    most recent 00124.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hawke, T. J. Articles by Garry, D. J. Search for Related Content PubMed PubMed Citation Articles by Hawke, T. J. Articles by Garry, D. J.

MUSCLE CELL BIOLOGY AND CELL MOTILITY

Xin, an actin binding protein, is expressed within muscle satellite cells and newly regenerated skeletal muscle fibers

¹School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada; ²Department of Biology, Colorado State University, Fort Collins, Colorado; ³Institute of Cell Biology, Department of Molecular Cell Biology, University of Bonn Ulrich-Haberland, Bonn, Germany; ⁴Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas; and ⁵Department of Medicine-Lillehei Heart Institute, University of Minnesota, Minneapolis, Minnesota

Submitted 29 March 2007 ; accepted in final form 10 September 2007

Xin is a muscle-specific actin binding protein of which its role and regulation within skeletal muscle is not well understood. Here we demonstrate that Xin mRNA is robustly upregulated (>16-fold) within 12 h of skeletal muscle injury and is localized to the muscle satellite cell population. RT-PCR confirmed the expression pattern of Xin during regeneration, as well as within primary muscle myoblast cultures, but not other known stem cell populations. Immunohistochemical staining of single myofibers demonstrate Xin expression colocalized with the satellite cell marker Syndecan-4 further supporting the mRNA expression of Xin in satellite cells. In situ hybridization of regenerating muscle 5–7 days postinjury illustrates Xin expression within newly regenerated myofibers. Promoter-reporter assays demonstrate that known myogenic transcription factors [myocyte enhancer factor-2 (MEF2), myogenic differentiation-1 (MyoD), and myogenic factor-5 (Myf-5)] transactivate Xin promoter constructs supporting the muscle-specific expression of Xin. To determine the role of Xin within muscle precursor cells, proliferation, migration, and differentiation analysis using Xin, short hairpin RNA (shRNA) were undertaken in C2C12 myoblasts. Reducing endogenous Xin expression resulted in a 26% increase (P < 0.05) in cell proliferation and a 20% increase (P < 0.05) in myoblast migratory capacity. Skeletal muscle myosin heavy chain protein levels were increased (P < 0.05) with Xin shRNA administration; however, this was not accompanied by changes in myoglobin protein (another marker of differentiation) nor overt morphological differences relative to differentiating control cells. Taken together, the present findings support the hypothesis that Xin is expressed within muscle satellite cells during skeletal muscle regeneration and is involved in the regulation of myoblast function.

muscle stem cell; cardiotoxin injury; myoblast; cmya1; muscular dystrophy