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Cellular Prion Protein Promotes Regeneration of Adult Muscle Tissue ,
Roberto Stella,1
Maria Lina Massimino,2
Marco Sandri,3,4
M. Catia Sorgato,1,2, and
Alessandro Bertoli1*
Department of Biological Chemistry,1
CNR Institute of Neuroscience,2
Department of Biomedical Sciences, University of Padova, Viale G. Colombo 3, 35131 Padua, Italy,3
Dulbecco Telethon Institute-Venetian Institute of Molecular Medicine, Via G. Orus, 2, 35129 Padua, Italy4
Received for publication 6 August 2009.
Revision received 2 September 2009.
Accepted for publication 22 July 2010.
Abstract:
It is now well established that the conversion of the cellularprion protein, PrPC, into its anomalous conformer, PrPSc, iscentral to the onset of prion disease. However, both the mechanismof prion-related neurodegeneration and the physiologic roleof PrPC are still unknown. The use of animal and cell modelshas suggested a number of putative functions for the protein,including cell signaling, adhesion, proliferation, and differentiation.Given that skeletal muscles express significant amounts of PrPCand have been related to PrPC pathophysiology, in the presentstudy, we used skeletal muscles to analyze whether the proteinplays a role in adult morphogenesis. We employed an in vivoparadigm that allowed us to compare the regeneration of acutelydamaged hind-limb tibialis anterior muscles of mice expressing,or not expressing, PrPC. Using morphometric and biochemicalparameters, we provide compelling evidence that the absenceof PrPC significantly slows the regeneration process comparedto wild-type muscles by attenuating the stress-activated p38pathway, and the consequent exit from the cell cycle, of myogenicprecursor cells. Demonstrating the specificity of this finding,restoring PrPC expression completely rescued the muscle phenotypeevidenced in the absence of PrPC.
* Corresponding author. Mailing address: University of Padua, Department of Biological Chemistry, Viale G. Colombo, 3, 35131 Padua, Italy. Phone: 39 049 8276150. Fax: 39 049 8073310. E-mail: alessandro.bertoli{at}unipd.it
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|Abstract »|Full Text »|PDF »
Published ahead of print on 2 August 2010. 
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