Inhibitory effect of AQP1 silencing on adhesion and angiogenesis in ectopic endometrial cells of mice with endometriosis through activating the Wnt signaling pathway

Abstract

The development mechanism of endometriosis remains unknown. Water channel aquaporin-1 (AQP1) enhances water flux across cell membranes, which is highly expressed and associated with cell migration, metastasis and angiogenesis in some human cancers. In this study, the role of the Wnt signaling pathway mediated by AQP1 in endometriosis was investigated, in a bid to provide new therapeutic targets for endometriosis. Microarray expression profiles were screened to acquired differentially expressed genes related to endometriosis. Mouse models with endometriosis were established and grouped. The level of endometriosis was evaluated by measurement of the volume of ectopic region. The expression of AQP1, pathway-related factors (Wnt1 and Wnt4), adhesion molecules (VCAM-1 and ICAM-1), invasive factors (MMP-2, MMP-9, TIMP-1 and TIMP-2), angiogenic factors (VEGF-A, VEGFR1 and VEGFR2) and apoptotic factors (Caspase-3, Caspase-9, Bax and BcL-2) was measured by RT-qPCR and western blot analysis. Furthermore, the role of AQP1 in adhesion, invasion, angiogenesis, and apoptosis of ectopic endometrial cells was determined by transfection of si-AQP1 plasmid. AQP1 was robustly expressed in endometriosis. AQP1 gene silencing alleviated the progression of endometriosis by activating the Wnt signaling pathway in mice with endometriosis. Specifically, silencing of AQP1 gene inhibited ectopic endometrial cell adhesion and invasion abilities, suppressed angiogenesis while promoted apoptosis. Collectively, the present study highlights the role of AQP1 in the regulation of the Wnt signaling pathway in endometriosis mouse models, suggesting that AQP1 could represent a new target aimed at improving the survival of patients with endometriosis.

Shen-Qi-Wan Protects the Renal Peritubular Capillary From Adenine-mediated Damage by Upregulating Aquaporin 1

“…Water channel protein-AQP1 maintains the osmotic balance in the renal cells and associates with cell migration and angiogenesis (32). Recently adequate evidence supported that inhibition of AQP1 relates to impaired migration, invasion and tubulogenesis in vitro (33). We have shown AQP1 knockdown inhibited cell migration and tube formation that was enhanced by SQW administration.…”

From Channels to Canonical Wnt Signaling: A Pathological Perspective

“…In addition, aquaporins also seem to have an important role in endometriosis. Shu et al observed that silencing of AQP1, which is upregulated in endometriosis disease, induces the activation of the Wnt signaling pathway that results in a decreased adhesion, invasion, and in the induction of apoptosis of ectopic cells [ 89 ].…”

Brassica Bioactives Could Ameliorate the Chronic Inflammatory Condition of Endometriosis

“…AQP1 might have a role in endometriosis via the Wnt/β-catenin signaling pathway. Hence, AQP1 gene silencing entails a decrease in the adhesion and invasion of ectopic endometrial cells, as well as a decrease in angiogenesis and an increase in the apoptosis rate of these cells [ 149 ]. In the same way, AQP5, whose expression is menstrual cycle-dependent [ 150 ], is more highly expressed in eutopic as compared with ectopic endometrial cells in women with endometriosis [ 151 ].…”

“…Their involvement in several intracellular signaling pathways as signal regulating factors (via transporting molecules or coupling with other proteins) [ 159 ] should be taken into account. Particularly, AQPs 1, 2, 8, and 9 could be related to endometriosis due to their participation in different signaling pathways such as Wnt/β-catenin, ERK/p38 MAPKm, and PI3K/Akt [ 149 , 152 , 154 ]. Hence, more studies are needed to reveal the actual signaling regulatory function of AQPs.…”