P27(Kip1) overexpression regulates IL-1 beta in the microenvironment of stem cells and eutopic endometriosis co-cultures

P27(Kip1) overexpression regulates IL-1 beta in the microenvironment of stem cells and eutopic endometriosis co-cultures

Author Gonçalves, Giovana Aparecida Autor UNIFESP Google Scholar
Invitti, Adriana Luckow Autor UNIFESP Google Scholar
Parreira, Rafael Martins Autor UNIFESP Google Scholar
Kopelman, Alexander Autor UNIFESP Google Scholar
Schor, Eduardo Autor UNIFESP Google Scholar
Girão, Manoel João Batista Castello Autor UNIFESP Google Scholar
Abstract Endometriosis is a gynecological benign chronic disease defined as the growth of endometrial glands and stroma in extra-uterine sites, most commonly implanted over visceral and peritoneal surfaces within the female pelvis causing inflammatory lesions. It affects around 10% of the female population and is often accompanied by chronic pelvic pain, adhesion formation and infertility. Therefore, endometriosis could be considered a "social disease", since it affects the quality of life, reproductivity and also has a socioeconomic impact. The expression of cell cycle and inflammatory proteins is modified in the endometriotic tissues. Immunostaining of glandular and stromal cells in endometrial biopsies obtained from patients with endometriosis compared with those of healthy control demonstrated that endometriotic tissues have lower levels of p27(kaP1) protein. Endometriosis endometrial cells cultures have also lower levels of p27(kip1) compared to health endometrial cells cultures and restore the cell cycle balance when transduced with an adenoviral vector carring the p27(kiP1) coding gene (Adp27EGFP). The low levels of p27(kip1) are related to the S phase in the cell cycle, whereas higher levels lead to a G1 cell cycle arrest. The inflammatory cytokine IL-1 beta was recently identified as another key protein in the endometriosis proliferation. This cytokine has elevated levels during the proliferative and secretory phases of the menstrual cycle. In endometriosis endometrial cells cultures the IL-beta stimulates the production of IL-6 and IL-8, increasing the cell proliferation and reducing the apoptosis and Bax expression in these cells. According to these remarks, this work aims to evaluate the inflammatory effects in vitro, but more next to what happens in a woman's body, associating endometrial cells with stem cells, thus mimicking the endometrial microenvironment, with gene therapy using Adp27, notoriously known as controller cell cycle, apoptosis and potent modulator of VEGF expression. (C) 2015 Elsevier Ltd. All rights reserved.
Keywords Endometriosis
Stem cells
xmlui.dri2xhtml.METS-1.0.item-coverage London
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 12-50479-8
Date 2017
Published in Cytokine. London, v. 89, p. 229-234, 2017.
ISSN 1043-4666 (Sherpa/Romeo, impact factor)
Publisher Academic Press Ltd- Elsevier Science Ltd
Extent 229-234
Origin http://dx.doi.org/10.1016/j.cyto.2015.12.015
Access rights Closed access
Type Article
Web of Science ID WOS:000391780000029
URI https://repositorio.unifesp.br/handle/11600/56499

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