Wnt Decoy Receptor (sLRP6E1E2) Induces Antifibrotic Effect Via Inhibition of Wnt Signaling in Keloid Scars

초록

Keloid scars are pathologic proliferations of the dermal skin layer resulting from excessive collagen deposition. The aberrant activation of the Wnt pathway signaling plays a critical role in keloid scars. In this study, we evaluated the therapeutic potential of a soluble Wnt receptor decoy in treatment of keloid scars. Therefore, we designed a Wnt antagonist sLRP6E1E2, and generated a replication-incompetent adenovirus (Ad), dE1-k35/sLRP6E1E2. We showed that γ-galactosidase expression confirmed the efficient transduction of dE1-K35/lacZ into human dermal fibroblasts. In addition, dE1-k35/ sLRP6E1E2 prevented Wnt-mediated stabilization of cytoplasmic γ-catenin and decreased Wnt/γ-catenin signaling. dE1-k35/ sLRP6E1E2 also inhibited Wnt-induced TGF-b up-regulation as well as Smad2/3 signaling pathway. Consistent with these data, the expression of ECM proteins was significantly decreased in keloid spheroids transduced with dE1-k35/sLRP6E1E2. These results suggest that the antifibrotic effect of sLRP6E1E2-expressing adenovirus may have therapeutic effects on keloids.