Wnt-β Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis and Dysfunction of the External Anal Sphincter

Abstract Wnt-β catenin is an important signaling pathway in the genesis of fibrosis in many organ systems. 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...

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Autores principales:	M. Raj Rajasekaran, Sadhana Kanoo, Johnny Fu, Valmik Bhargava, Ravinder K. Mittal
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f54fec09083f4b0893cc627f851aafa1
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spelling	oai:doaj.org-article:f54fec09083f4b0893cc627f851aafa12021-12-02T16:06:01ZWnt-β Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis and Dysfunction of the External Anal Sphincter10.1038/s41598-017-01131-62045-2322https://doaj.org/article/f54fec09083f4b0893cc627f851aafa12017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01131-6https://doaj.org/toc/2045-2322Abstract Wnt-β catenin is an important signaling pathway in the genesis of fibrosis in many organ systems. 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-β) and immunostaining for β 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 β catenin activation and molecular studies revealed 1.5–2 fold increase in the levels of markers of fibrosis. Local injection of sFRP-2 attenuated the β 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.M. Raj RajasekaranSadhana KanooJohnny FuValmik BhargavaRavinder K. MittalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q M. Raj Rajasekaran Sadhana Kanoo Johnny Fu Valmik Bhargava Ravinder K. Mittal Wnt-β Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis and Dysfunction of the External Anal Sphincter
description	Abstract Wnt-β catenin is an important signaling pathway in the genesis of fibrosis in many organ systems. 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-β) and immunostaining for β 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 β catenin activation and molecular studies revealed 1.5–2 fold increase in the levels of markers of fibrosis. Local injection of sFRP-2 attenuated the β 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.
format	article
author	M. Raj Rajasekaran Sadhana Kanoo Johnny Fu Valmik Bhargava Ravinder K. Mittal
author_facet	M. Raj Rajasekaran Sadhana Kanoo Johnny Fu Valmik Bhargava Ravinder K. Mittal
author_sort	M. Raj Rajasekaran
title	Wnt-β Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis and Dysfunction of the External Anal Sphincter
title_short	Wnt-β Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis and Dysfunction of the External Anal Sphincter
title_full	Wnt-β Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis and Dysfunction of the External Anal Sphincter
title_fullStr	Wnt-β Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis and Dysfunction of the External Anal Sphincter
title_full_unstemmed	Wnt-β Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis and Dysfunction of the External Anal Sphincter
title_sort	wnt-β catenin signaling pathway: a major player in the injury induced fibrosis and dysfunction of the external anal sphincter
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f54fec09083f4b0893cc627f851aafa1
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Wnt-β Catenin Signaling Pathway: A Major Player in the Injury Induced Fibrosis and Dysfunction of the External Anal Sphincter

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