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Our goal was to examine the role of Wnt pathway in the external anal sphincter (EAS) injury-related fibrosis and muscle dysfunction. New Zealand White female rabbits were subjected to surgical EAS myotomy and administered local injections of either a Wnt antagonist (sFRP-2; daily for 7 days) or saline. Anal canal pressure and EAS length-tension (L-T) were measured for 15 weeks after which the animals were sacrificed. Anal canal was harvested and processed for histochemical studies (Masson trichrome stain), molecular markers of fibrosis (collagen and transforming growth factor-\u03b2) and immunostaining for \u03b2 catenin. Surgical myotomy of the EAS resulted in significant impairment in anal canal pressure and EAS muscle L-T function. Following myotomy, the EAS muscle was replaced with fibrous tissue. Immunostaining revealed \u03b2 catenin activation and molecular studies revealed 1.5\u20132 fold increase in the levels of markers of fibrosis. Local injection of sFRP-2 attenuated the \u03b2 catenin activation and fibrosis. EAS muscle content and function was significantly improved following sFRP-2 treatment. Our studies suggest that upregulation of Wnt signaling is an important molecular mechanism of injury related EAS muscle fibrosis and sphincter dysfunction.<\/jats:p>","DOI":"10.1038\/s41598-017-01131-6","type":"journal-article","created":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T14:14:30Z","timestamp":1491920070000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Wnt-\u03b2 Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis and Dysfunction of the External Anal Sphincter"],"prefix":"10.1038","volume":"7","author":[{"given":"M. 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