Exosome-mediated microRNA-138 and vascular endothelial growth factor in endometriosis through inflammation and apoptosis via the nuclear factor-κB signaling pathway

Zhang,Aifeng; Wang,Guoyun; Jia,Lihua; Su,Tao; Zhang,Lili

doi:10.3892/ijmm.2018.3980

Exosome-mediated microRNA-138 and vascular endothelial growth factor in endometriosis through inflammation and apoptosis via the nuclear factor-κB signaling pathway

Authors:
- Aifeng Zhang
- Guoyun Wang
- Lihua Jia
- Tao Su
- Lili Zhang
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Affiliations: Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Obstetrics and Gynecology, Tongzhou Maternal and Child Health Hospital of Beijing, Beijing 101100, P.R. China, Department of Obstetrics and Gynecology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China
Published online on: November 6, 2018 https://doi.org/10.3892/ijmm.2018.3980
Pages: 358-370
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Endometriosis (Ems) is a condition that refers to the ectopic implantation and growth of endometrial tissue outside the uterine cavity. The aim of the present study was to investigate the role of microRNA‑138 (miR‑138) in Ems and the possible underlying mechanism. Flow cytometry was measured CD11b level, cell proliferation was measured using MTT assay and lactate dehydrogenase (LDH) assays was analyzed using LDH activity kits. Cell apoptosis was measured using Annexin V‑FITC/PI double staining apoptosis detection kit and DAPI assays. ELISA assay and western blot analysis were used to measure protein expression determination. It was first observed that miR‑138 expression was markedly downregulated and the CD11b level was reduced in Ems mice compared with the control group. Subsequently, miR‑138 expression was downregulated in the uterine endothelial cells co‑cultured with THP‑1 cells, which resulted in decreased apoptosis and increased inflammation in the uterine endothelial cells. By contrast, upregulation of miR‑138 by mimic transfection increased the proliferation and reduced inflammation in uterine endothelial cells. In addition, in the co‑culture of uterine endothelial and THP‑1 cells, downregulation of miR‑138 induced the expression of nuclear factor (NF)‑κB and vascular endothelial growth factor (VEGF) proteins in THP‑1 cells. Furthermore, treatment with an NF‑κB inhibitor and downregulation of miR‑138 in the co‑culture of uterine endothelial and THP‑1 cells reduced inflammation. VEGF inhibitor treatment and downregulation of miR‑138 in this cell co‑culture promoted the proliferation of uterine endothelial cells. These results suggested that uterine endothelial cells promoted miR‑138 to induce exosome‑mediated inflammation and apoptosis in Ems through the VEGF/NF‑κB signaling pathway.

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