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骨膜蛋白通过整合素连接激酶1/蛋白激酶B信号通路增强人子宫内膜基质细胞的迁移、侵袭和黏附。

Periostin Enhances Migration, Invasion, and Adhesion of Human Endometrial Stromal Cells Through Integrin-Linked Kinase 1/Akt Signaling Pathway.

作者信息

Xu Xiaoxuan, Zheng Qiaomei, Zhang Zongzheng, Zhang Xiaolei, Liu Ruihan, Liu Peishu

机构信息

Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China.

Department of Orthopedics, Taishan Medical University, Tai'an, Shandong, China.

出版信息

Reprod Sci. 2015 Sep;22(9):1098-106. doi: 10.1177/1933719115572481. Epub 2015 Mar 9.

Abstract

Although our previous study confirmed that periostin (PN) was overexpressed in the eutopic and ectopic endometrial stroma of women with endometriosis by immunohistochemitry, the role of PN in the pathophysiology of endometriosis remains unknown. Thus, we aimed to investigate the effects of PN on endometrial stromal cells (ESCs) migration, invasion, adhesion, and proliferation and to further study the mechanism under this process. Eutopic (EuSCs), ectopic (EcSCs), and normal ESCs (NSCs) were isolated and cultured. We evaluated the above-mentioned biology behaviors and the expression of PN, integrin-linked kinase 1 (ILK1), and phospho-Akt (p-Akt) in NSCs, EuSCs as well as EcSCs before and after receiving PN small-interfering RNA (siRNA). The protein and messenger RNA (mRNA) levels of PN were upregulated in EuSCs (P < .05; P = .2261 in proliferative phase and P = .3385 in secretory phase) and EcSCs (P < .001; P < .001 in proliferative phase and P < .05 in secretory phase) compared with NSCs, although there was no significant difference in PN mRNA between EuSCs and NSCs. In EcSCs, abilities of migration, invasion, and adhesion and the expressions of ILK1 and p-Akt were enhanced; and all of those were downregulated after PN siRNA interference. Thus, PN enhanced ESCs migration, invasion, and adhesion due to the ILK1/Akt signal pathway. As an agonist in the development and progression of endometriosis, PN may be a new clinical treatment target of endometriosis.

摘要

尽管我们之前的研究通过免疫组织化学证实,骨膜蛋白(PN)在子宫内膜异位症患者的在位和异位子宫内膜基质中过表达,但PN在子宫内膜异位症病理生理学中的作用仍不清楚。因此,我们旨在研究PN对子宫内膜基质细胞(ESC)迁移、侵袭、黏附和增殖的影响,并进一步探讨这一过程的机制。分离并培养在位(EuSCs)、异位(EcSCs)和正常ESC(NSCs)。我们评估了上述生物学行为以及在接受PN小干扰RNA(siRNA)前后NSCs、EuSCs和EcSCs中PN、整合素连接激酶1(ILK1)和磷酸化Akt(p-Akt)的表达。与NSCs相比,EuSCs(增殖期P <.05;增殖期P = 0.2261,分泌期P = 0.3385)和EcSCs(增殖期P <.001;增殖期P <.)中PN的蛋白质和信使RNA(mRNA)水平上调。001,分泌期P <.05),尽管EuSCs和NSCs之间的PN mRNA没有显著差异。在EcSCs中,迁移、侵袭和黏附能力以及ILK1和p-Akt的表达增强;PN siRNA干扰后所有这些均下调。因此,PN通过ILK1/Akt信号通路增强了ESC的迁移、侵袭和黏附。作为子宫内膜异位症发生和发展的激动剂,PN可能是子宫内膜异位症新的临床治疗靶点。

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