Secreted frizzled related protein 1 (Sfrp1) and Wnt signaling in innervated and denervated skeletal muscle.

Wnts are secreted proteins with functions in differentiation, development and cell proliferation. Wnt signaling has also been implicated in neuromuscular junction formation and may function in synaptic plasticity in the adult as well. Secreted frizzled-related proteins (Sfrps) such as Sfrp1 can function as inhibitors of Wnt signaling. In the present study a potential role of Wnt signaling in denervation was examined by comparing the expression levels of Sfrp1 and key proteins in the canonical Wnt pathway, Dishevelled, glycogen synthase kinase 3beta and beta-catenin, in innervated and denervated rodent skeletal muscle. Sfrp1 mRNA and immunoreactivity were found to be up-regulated in mouse hemidiaphragm muscle following denervation. Immunoreactivity, detected by Western blots, and mRNA, detected by Northern blots, were both expressed in extrasynaptic as well as perisynaptic parts of the denervated muscle. Immunoreactivity on tissue sections was, however, found to be concentrated postsynaptically at neuromuscular junctions. Using beta-catenin levels as a readout for canonical Wnt signaling no evidence for decreased canonical Wnt signaling was obtained in denervated muscle. A role for Sfrp1 in denervated muscle, other than interfering with canonical Wnt signaling, is discussed.