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深部浸润型子宫内膜异位症和子宫内膜腺癌中肌生成抑制蛋白及其受体信使核糖核酸表达水平较高。

Deep Infiltrating Endometriosis and Endometrial Adenocarcinoma Express High Levels of Myostatin and Its Receptors Messenger RNAs.

作者信息

Carrarelli Patrizia, Funghi Lucia, Ciarmela Pasquapina, Centini Gabriele, Reis Fernando M, Dela Cruz Cynthia, Mattei Alberto, Vannuccini Silvia, Petraglia Felice

机构信息

1 Department of Molecular and Developmental Medicine, Obstetrics and Gynecology, University of Siena, Siena, Italy.

2 Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy.

出版信息

Reprod Sci. 2017 Dec;24(12):1577-1582. doi: 10.1177/1933719117698579. Epub 2017 Mar 27.

Abstract

Myostatin is a growth factor member of the transforming growth factor β superfamily, which is known to play major roles in cell proliferation and differentiation. The present study investigated the messenger RNA (mRNA) expression of myostatin and myostatin receptors (activin receptor-like kinase 4 [ALK4], transforming growth factor (TGF)-β type I receptor kinase [ALK5] and activin receptor type IIB [ActRIIB]) in endometrium of healthy women during menstrual cycle as well as in benign (endometriosis, polyps) and malignant (endometrial adenocarcinoma) conditions. Endometrial specimens were collected by hysteroscopy, whereas endometriotic lesions were collected by laparoscopy, and adenocarcinomas were sampled after hysterectomy. Total RNA was extracted from tissue homogenates, and gene expression was assessed by quantitative real-time polymerase chain reaction. Myostatin and myostatin receptors mRNAs were expressed by healthy endometrium throughout the menstrual cycle, with no differences between the proliferative and secretory phase. The highest myostatin mRNA expression was found in patients with deep infiltrating endometriosis (DIE) and in endometrial carcinoma; expression was also found in ovarian endometrioma (OMA ) and endometrial polyps. Myostatin receptors mRNA expression was higher in DIE and adenocarcinomas compared to control endometrium. The expression of ALK5 and ActRIIB in OMA was higher than in controls, whereas polyps had an increased expression of ALK5 mRNA. In conclusion, the present data showed for the first time the expression of myostatin in healthy endometrium and a higher expression in endometriosis and endometrial cancer, suggesting myostatin involvement in human endometrial physiology and related pathologies.

摘要

肌肉生长抑制素是转化生长因子β超家族的一种生长因子成员,已知其在细胞增殖和分化中起主要作用。本研究调查了健康女性月经周期子宫内膜以及良性(子宫内膜异位症、息肉)和恶性(子宫内膜腺癌)情况下肌肉生长抑制素及其受体(激活素受体样激酶4 [ALK4]、转化生长因子(TGF)-β I型受体激酶[ALK5]和激活素IIB型受体[ActRIIB])的信使核糖核酸(mRNA)表达。子宫内膜标本通过宫腔镜检查收集,而子宫内膜异位症病变通过腹腔镜检查收集,腺癌在子宫切除术后取样。从组织匀浆中提取总RNA,并通过定量实时聚合酶链反应评估基因表达。在整个月经周期中,健康子宫内膜均表达肌肉生长抑制素及其受体的mRNA,增殖期和分泌期之间无差异。在深部浸润性子宫内膜异位症(DIE)患者和子宫内膜癌患者中发现肌肉生长抑制素mRNA表达最高;在卵巢子宫内膜异位囊肿(OMA)和子宫内膜息肉中也发现了表达。与对照子宫内膜相比,DIE和腺癌中肌肉生长抑制素受体mRNA表达更高。OMA中ALK5和ActRIIB的表达高于对照组,而息肉中ALK5 mRNA表达增加。总之,本数据首次显示了肌肉生长抑制素在健康子宫内膜中的表达以及在子宫内膜异位症和子宫内膜癌中的高表达,提示肌肉生长抑制素参与人类子宫内膜生理及相关病理过程。

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