Cellular prion protein promotes regeneration of adult muscle tissue.
It is now well established that the conversion of the cellular prion protein, PrP(C), into its anomalous conformer, PrP(Sc), is central to the onset of prion disease. However, both the mechanism of prion-related neurodegeneration and the physiologic role of PrP(C) are still unknown. The use of animal and cell models has suggested a number of putative functions for the protein, including cell signaling, adhesion, proliferation, and differentiation. Given that skeletal muscles express significant amounts of PrP(C) and have been related to PrP(C) pathophysiology, in the present study, we used skeletal muscles to analyze whether the protein plays a role in adult morphogenesis. We employed an in vivo paradigm that allowed us to compare the regeneration of acutely damaged hind-limb tibialis anterior muscles of mice expressing, or not expressing, PrP(C). Using morphometric and biochemical parameters, we provide compelling evidence that the absence of PrP(C) significantly slows the regeneration process compared to wild-type muscles by attenuating the stress-activated p38 pathway, and the consequent exit from the cell cycle, of myogenic precursor cells. Demonstrating the specificity of this finding, restoring PrP(C) expression completely rescued the muscle phenotype evidenced in the absence of PrP(C).
Stella
Roberto
R
University of Padua, Department of Biological Chemistry, Padua, Italy.
Massimino
Maria Lina
ML
Sandri
Marco
M
Sorgato
M Catia
MC
Bertoli
Alessandro
A
D000818:Animals; D002453:Cell Cycle; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D024510:Muscle Development / Q000235:genetics / Q000502:physiology; D018482:Muscle, Skeletal / Q000254:growth & development / Q000293:injuries / Q000502:physiology*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000502:physiology; D010641:Phenotype; D018621:PrPC Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012038:Regeneration / Q000235:genetics / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018621:PrPC Proteins; D048051:p38 Mitogen-Activated Protein Kinases