Open Access

MicroRNA-1291 promotes endometrial fibrosis by regulating the ArhGAP29-RhoA/ROCK1 signaling pathway in a murine model

  • Authors:
    • Qian Xu
    • Hua Duan
    • Lu Gan
    • Xin Liu
    • Fang Chen
    • Xue Shen
    • Yi‑Qun Tang
    • Sha Wang
  • View Affiliations

  • Published online on: August 10, 2017     https://doi.org/10.3892/mmr.2017.7210
  • Pages: 4501-4510
  • Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Intrauterine adhesions (IUAs) are caused by endometrial damage and are associated with a poor pregnancy prognosis including infertility, oligomenorrhea and recurrent pregnancy loss. Understanding the pathogenesis of IUAs may help prevent and treat this condition more effectively. The aim of the current study was to investigate the function of microRNA‑1291 (miR‑1291) during the development of IUAs following endometrial damage and elucidate the potential molecular mechanisms involved. The expression of Rho GTPase activating protein 29 (ArhGAP29), a putative target mRNA of miR‑1291, was determined by immunohistochemical staining of human endometrial tissue from patients with IUAs and compared with normal endometrial tissues. ArhGAP29 expression was significantly decreased in endometrial tissues with IUAs compared with normal endometrium. Additionally, a murine IUAs model was develo­ped and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) demonstrated that miR‑1291 levels were significantly increased in the uterine tissue and plasma of the IUAs group compared with the normal mice. Furthermore, an miR‑1291 antagomir was injected into the uterine cavity of experimental IUAs mice to block miR‑1291. Hematoxylin and eosin and Masson's stain revealed that blocking miR‑1291 significantly ameliorated endometrial fibrosis. Furthermore, levels of epithelial mesenchymal transition (EMT)‑associated proteins, and ArhGAP29‑RhoA/Rho‑associated coiled coil containing protein kinase 1 (ROCK1) were measured in uterine tissue by western blot, RT‑qPCR analysis and immunofluorescence staining. Levels of the mesenchymal marker proteins, vimentin and N‑cadherin, were increased in the IUAs group mice, accompanied by a relative decrease in the epithelial marker proteins, cytokeratin and E‑cadherin compared with normal murine endometrium. miR‑1291 inhibition decreased RhoA/ROCK1 expression in the EMT pathway, but increased ArhGAP29 expression. Taken together, the findings indicate that miR‑1291 acts upstream of ArhGAP29 to negatively regulate the RhoA/ROCK1 EMT pathway, ultimately leading to endometrial fibrosis. These studies may provide new potential therapeutic options and pave the way to use circulating miR‑1291 as a clinical biomarker of endometrial fibrosis.

Related Articles

Journal Cover

October-2017
Volume 16 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Xu Q, Duan H, Gan L, Liu X, Chen F, Shen X, Tang YQ and Wang S: MicroRNA-1291 promotes endometrial fibrosis by regulating the ArhGAP29-RhoA/ROCK1 signaling pathway in a murine model. Mol Med Rep 16: 4501-4510, 2017
APA
Xu, Q., Duan, H., Gan, L., Liu, X., Chen, F., Shen, X. ... Wang, S. (2017). MicroRNA-1291 promotes endometrial fibrosis by regulating the ArhGAP29-RhoA/ROCK1 signaling pathway in a murine model. Molecular Medicine Reports, 16, 4501-4510. https://doi.org/10.3892/mmr.2017.7210
MLA
Xu, Q., Duan, H., Gan, L., Liu, X., Chen, F., Shen, X., Tang, Y., Wang, S."MicroRNA-1291 promotes endometrial fibrosis by regulating the ArhGAP29-RhoA/ROCK1 signaling pathway in a murine model". Molecular Medicine Reports 16.4 (2017): 4501-4510.
Chicago
Xu, Q., Duan, H., Gan, L., Liu, X., Chen, F., Shen, X., Tang, Y., Wang, S."MicroRNA-1291 promotes endometrial fibrosis by regulating the ArhGAP29-RhoA/ROCK1 signaling pathway in a murine model". Molecular Medicine Reports 16, no. 4 (2017): 4501-4510. https://doi.org/10.3892/mmr.2017.7210