RESUMEN
Epithelial-mesenchymal transition (EMT) plays a significant part in the pathogenesis of endometriosis by facilitating the migration and invasion abilities of cells. Integrin-linked kinase (ILK) increases the cell migration and invasion abilities by inducing the EMT. Eutopic and control endometrial stromal cells (EuSCs and CSCs) were isolated and cultured. Cell migration and invasion abilities were detected by transwell assays. Levels of proteins were detected by Western blot. EuSCs showed higher levels of ILK, N-cadherin, vimentin and stronger migration and invasion abilities. After transfection of siRNA-ILK, E-cadherin and keratin levels were increased while N-cadherin and vimentin levels were decreased in EuSCs. Besides that, the migration and invasion abilities of EuSCs were significantly decreased after transfection of siRNA-ILK. On the contrary, levels of ILK, N-cadherin and vimentin were increased while levels of E-cadherin and keratin were decreased simultaneously after transfecting CSCs with pEGFP-C1-ILK. Simultaneously, the migration and invasion abilities of CSCs were increased after transfection of pEGFP-C1-ILK. Our study verified that high expression of ILK enhanced the migration and invasion abilities of ESCs by facilitating the EMT. Given that ILK played crucial roles in the pathogenesis of endometriosis, it may be considered as a promising targeted therapy for endometriosis.
Asunto(s)
Endometriosis/etiología , Endometrio/citología , Transición Epitelial-Mesenquimal , Proteínas Serina-Treonina Quinasas/fisiología , Adulto , Movimiento Celular , Femenino , Humanos , Persona de Mediana Edad , Células del Estroma/fisiología , Adulto JovenRESUMEN
Although periostin was confirmed to facilitate the pathogenesis of endometriosis by enhancing the migration, invasion, and adhesion of human endometrial stromal cells (ESCs), its effect on the endometrial epithelial cells (EECs) is still unknown. The current study aimed to determine whether periostin enhanced the epithelial-mesenchymal transition (EMT) of EECs. EECs were isolated from 12 women with endometriosis. The migration and invasion abilities of EECs were evaluated by transwell assays. Expressions of proteins were detected by western blot. After treatment with periostin, the migration and invasion abilities of EECs were enhanced. Additionally, E-cadherin and keratin were downregulated while N-cadherin and vimentin were upregulated in EECs. Simultaneously, levels of ILK, p-Akt, slug, and Zeb1 were all upregulated in EECs. After silencing the expression of ILK in EECs, levels of p-Akt, slug, Zeb1, N-cadherin, and vimentin were downregulated while E-cadherin and keratin were upregulated. Although periostin weakened the above effects in EECs after silencing the expression of ILK, it failed to induce the EMT of EECs. Thus, periostin enhanced invasion and migration abilities of EECs and facilitated the EMT of EECs through ILK-Akt signaling pathway. Playing a pivotal role in the pathogenesis of endometriosis, periostin may be a new clinical therapy target for endometriosis.
Asunto(s)
Moléculas de Adhesión Celular/genética , Endometriosis/genética , Transición Epitelial-Mesenquimal/genética , Proteína Oncogénica v-akt/genética , Proteínas Serina-Treonina Quinasas/genética , Moléculas de Adhesión Celular/antagonistas & inhibidores , Moléculas de Adhesión Celular/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Tumores Estromáticos Endometriales/genética , Tumores Estromáticos Endometriales/patología , Endometriosis/metabolismo , Endometriosis/patología , Endometrio/metabolismo , Endometrio/patología , Células Epiteliales/metabolismo , Células Epiteliales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Invasividad Neoplásica/genética , Invasividad Neoplásica/patología , Proteína Oncogénica v-akt/biosíntesis , Proteínas Serina-Treonina Quinasas/biosíntesis , Transducción de Señal/genéticaRESUMEN
BACKGROUND: Endometrial polyps (EP) and endometriosis are both estrogen-dependent overgrowths of the endometrium. Several studies have shown a higher frequency of EP in endometriosis patients when compared with women without endometriosis. Therefore, we performed a meta-analysis to investigate the risk of EP in women with endometriosis. METHODS: This meta-analysis searched for articles published between 1964 and 2014 in PubMed, Embase, and Cochrane Library, as well as in Chinese databases, including CNKI, VIP and Wanfang, regarding the association between endometriosis and EP. Nine cohort studies and one case-control study including 2896 women were included in this meta-analysis. The EP risk was evaluated using relative risk (RR) with a 95% confidence interval (CI). Heterogeneity, small study effect and publication bias were assessed using Higgins I(2), sensitivity analysis and funnel plots, respectively. RESULTS: The risk of EP increased in women with endometriosis compared with those without endometriosis (the pooled RR, 2.81; 95% CI, 2.48-3.18). No significant heterogeneity, small study effect or publication bias was found. The risk of EP slightly increased in women with endometriosis at stages 2-4 compared with those at stage 1 (Pooled effect size: stage 2 versus stage 1, RR, 1.22, 95% CI, 1.04 - 1.42; stage 3 versus stage 1, RR, 1.23, 95% CI, 1.06-1.42; stage 4 versus stage 1, RR, 1.29, 95% CI, 1.11-1.51; stages 2-4 versus stage 1, RR, 1.24, 95% CI, 1.10-1.40); however, no significantly different risk of EP in women with endometriosis existed between the other stages. CONCLUSION: The results suggest that it is important to identify whether patients with endometriosis also have EP and then remove any coexisting EP via hysteroscopy, especially for infertile patients. This process will be clinically helpful to treat endometriosis-related infertility in patients with endometriosis, especially for those with endometriosis that is more serious than stage 1.