PRL-3 Is Involved in Estrogen- and IL-6–Induced Migration of Endometrial Stromal Cells From Ectopic Endometrium

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PRL-3 protein was highly expressed in ectopic endometrial stromal cells and was involved in estrogen- and IL-6–induced cell migration via the PTEN-AKT pathway.

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This study examined the role of phosphatase of regenerating liver-3 (PRL-3) in how 17β-estradiol and interleukin-6 induce migration of endometrial stromal cells (ESCs) derived from ectopic endometrium. Ectopic and eutopic endometrial tissues were collected from patients with endometriosis, PRL-3 expression was assessed by immunohistochemistry, and ESCs were treated with 17β-estradiol, progesterone, IL-6, or the PRL-3 inhibitor sodium orthovanadate, with migration measured by scratch wound assay and PRL-3/PI3K–AKT/PTEN pathway signaling evaluated by qRT-PCR and Western blotting. PRL-3 was highly expressed in ESCs and endometrial glandular cells in ectopic tissue, estradiol and IL-6 increased PRL-3 expression and both estradiol- and IL-6-enhanced migration were abrogated by sodium orthovanadate; progesterone inhibited PRL-3, and the inhibitor increased PTEN while reducing p-AKT activation. The paper’s key limitation is that it uses in vitro stromal cell migration and pathway modulation rather than in vivo demonstration of PRL-3–dependent migration. This paper is centrally about endometriosis — it focuses on PRL-3 involvement in estrogen- and IL-6–induced migration of endometrial stromal cells from ectopic endometrium.

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Abstract

ObjectiveTo investigate the role of phosphatase of regenerating liver-3 (PRL-3) in the 17β-estradiol (E2)- and interleukin 6 (IL-6)-induced migration of endometrial stromal cells (ESCs) from ectopic endometrium.MethodsEctopic endometrial tissues were collected from patients with endometriosis, and PRL-3 expression in ectopic and eutopic endometrium was examined by immunohistochemistry. Endometrial stromal cells isolated from ectopic endometrium were treated with E2, progesterone (P), IL-6, or sodium orthovanadate (Sov) to inhibit PRL-3. Total RNA and protein were extracted from ESCs after treatment for quantitative real-time polymerase chain reaction and Western blot analyses. Cell migration was assessed using a scratch wound assay.ResultsPhosphatase of regenerating liver 3 protein was highly expressed in the endometrial glandular cells (EGCs) and ESCs in ectopic endometrium, whereas its weak expression was observed only in EGCs in eutopic endometrium. Both E2 and IL-6 treatment significantly increased PRL-3 messenger RNA and protein expression, and P treatment significantly inhibited PRL-3 expression. However, E2-induced PRL-3 expression in ESCs from ectopic endometrium was significantly blocked by IL-6 antibody. Moreover, E2- and IL-6-enhanced cell migration was completely abrogated by Sov treatment. Furthermore, Sov treatment could significantly promote PTEN expression but inhibit E2- and IL-6-induced p-AKT activation.ConclusionPhosphatase of regenerating liver 3 plays a key role in the E2- and IL-6-induced migration of ESCs from ectopic endometrium, a process that is involved in the PTEN-AKT signaling pathway.
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Abstract

Objective: To investigate the role of phosphatase of regenerating liver-3 (PRL-3) in the 17β-estradiol (E2)- and interleukin 6 (IL-6)-induced migration of endometrial stromal cells (ESCs) from ectopic endometrium. Methods: Ectopic endometrial tissues were collected from patients with endometriosis, and PRL-3 expression in ectopic and eutopic endometrium was examined by immunohistochemistry. Endometrial stromal cells isolated from ectopic endometrium were treated with E2, progesterone (P), IL-6, or sodium orthovanadate (Sov) to inhibit PRL-3. Total RNA and protein were extracted from ESCs after treatment for quantitative real-time polymerase chain reaction and Western blot analyses. Cell migration was assessed using a scratch wound assay. Results: Phosphatase of regenerating liver 3 protein was highly expressed in the endometrial glandular cells (EGCs) and ESCs in ectopic endometrium, whereas its weak expression was observed only in EGCs in eutopic endometrium. Both E2 and IL-6 treatment significantly increased PRL-3 messenger RNA and protein expression, and P treatment significantly inhibited PRL-3 expression. However, E2-induced PRL-3 expression in ESCs from ectopic endometrium was significantly blocked by IL-6 antibody. Moreover, E2- and IL-6-enhanced cell migration was completely abrogated by Sov treatment. Furthermore, Sov treatment could significantly promote PTEN expression but inhibit E2- and IL-6-induced p-AKT activation. Conclusion: Phosphatase of regenerating liver 3 plays a key role in the E2- and IL-6-induced migration of ESCs from ectopic endometrium, a process that is involved in the PTEN-AKT signaling pathway. Similar content being viewed by others

References

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