Aberrant levels of Wnt/β-catenin pathway components in a rat model of endometriosis.

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This study found increased Wnt4, Wnt7b, nuclear β-catenin, and galectin-3, along with decreased Gsk3beta and E-cadherin, in a rat endometriosis model, indicating heightened Wnt/β-catenin pathway activity.

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The study investigated Wnt/β-catenin pathway activity in a rat model of peritoneal endometriosis by analyzing mRNA expression of pathway-related molecules in endometriotic lesions and assessing β-catenin localization by staining. The authors found increased Wnt4 and Wnt7b mRNA, decreased Gsk3beta and E-cadherin mRNA, no mRNA differences for β-catenin or Fzd2, but a significant increase in nuclear β-catenin and higher rates of stromal and nuclear β-catenin localization in endometriotic lesions versus endometrium, alongside increased galectin-3 expression. A major caveat is that the paper reports expression changes and localization differences without detailing functional causality or angiogenic outcome measures. This paper is centrally about endometriosis — it directly evaluates aberrant Wnt/β-catenin pathway component expression and nuclear β-catenin activation in a rat endometriosis model.

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Abstract

Endometriosis is a benign gynecological disease affecting approximately 10-15% of women of reproductive age and 25-50% of all infertile women. It is characterized by the presence of glands and/or endometrial stroma outside the uterine cavity. Angiogenesis is a crucial process for the development and maintenance of endometriotic lesions. The Wnt/β-catenin pathway is a major promoter of angiogenesis in both physiological and pathological conditions. In the present study, we evaluated the expression of molecules related to the Wnt/β-catenin pathway in a rat model of peritoneal endometriosis. mRNA analyses showed significantly increased expression of Wnt4 and Wnt7b and decreased expression of Gsk3beta and E-cadherin in endometriotic lesions. However, there were no differences in β-catenin and Fzd2 mRNA expression. In addition, we observed a significant increase of nuclear β-catenin in endometriotic lesions, a hallmark of Wnt/ β-catenin pathway activation. Stromal β-catenin staining was found in 45.4% of endometrial tissues and 77.8% of endometriotic lesions. β-catenin nuclear localization was found in 18.2% of the endometrial tissues and 33.3% of endometriotic lesions. Finally, the expression of galectin-3, a regulator of this pathway, was increased in endometriosis. In summary, this pattern of Wnt/β-catenin components expression suggests an increased activity of this pathway in endometriosis.
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Aberrant levels of Wnt/β-catenin pathway components in a rat model of endometriosis R�mulo Medina de Mattos1, Paula Rodrigues Pereira1, Eliane Gouv�a de Oliveira Barros1, Julianna Henriques da Silva1, Celia Yelimar Palmero1, Nath�lia Meireles da Costa2, Luis Felipe Ribeiro Pinto2, Etel Rodrigues Pereira Gimba2, F�bio Hecht3, Luciana Bueno Ferreira4, Daniel Escorsim Machado5, Felipe Leite de Oliveira1 and Luiz Eurico Nasciutti1 1Institute of Biomedical Sciences, Federal University of Rio de Janeiro, 2National Cancer Institute, 3Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil, 4Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal and 5Health and Biological Sciences Center, Pharmacy College, State University of East Zone, Rio de Janeiro, Brazil Offprint requests to: Dr. Luiz Eurico Nasciutti, Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Ci�ncias Biom�dicas, Universidade Federal do Rio de Janeiro, Cidade Universit�ria - Ilha do Fund�o 21941 - 590 Rio de Janeiro, RJ, Brazil. e-mail: [email protected] or [email protected] Summary. Endometriosis is a benign gynecological disease affecting approximately 10-15% of women of reproductive age and 25-50% of all infertile women. It is characterized by the presence of glands and/or endometrial stroma outside the uterine cavity. Angiogenesis is a crucial process for the development and maintenance of endometriotic lesions. The Wnt/β-catenin pathway is a major promoter of angiogenesis in both physiological and pathological conditions. In the present study, we evaluated the expression of molecules related to the Wnt/β-catenin pathway in a rat model of peritoneal endometriosis. mRNA analyses showed significantly increased expression of Wnt4 and Wnt7b and decreased expression of Gsk3beta and E-cadherin in endometriotic lesions. However, there were no differences in β-catenin and Fzd2 mRNA expression. In addition, we observed a significant increase of nuclear β-catenin in endometriotic lesions, a hallmark of Wnt/ β -catenin pathway activation. Stromal β-catenin staining was found in 45.4% of endometrial tissues and 77.8% of endometriotic lesions. β-catenin nuclear localization was found in 18.2% of the endometrial tissues and 33.3% of endometriotic lesions. Finally, the expression of galectin-3, a regulator of this pathway, was increased in endometriosis. In summary, this pattern of Wnt/β-catenin components expression suggests an increased activity of this pathway in endometriosis. Histol Histopathol 31, 933-942 (2016) Key words: Endometriosis, Wnt pathway, β-catenin, Galectin-3, Rat models DOI: 10.14670/HH-11-730

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Wnt Signaling Pathway Animals beta Catenin beta Catenin Blotting, Western Disease Models, Animal Endometriosis Endometriosis Female Fluorescent Antibody Technique Rats Rats, Sprague-Dawley Real-Time Polymerase Chain Reaction Transcriptome Wnt Signaling Pathway

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