Department of Reproductive Medicine, General Hospital of Ningxia Medical University (The First Clinical Medical College of Ningxia Medical University), 804 Shengli Street, Xingqing Square, Yinchuan, 750004, Ningxia, China.
Department of Human Anatomy, Histology and Embryology, School of Basic Medicine, Ningxia Medical University, Yinchuan, 750004, Ningxia, China.
Sci Rep. 2024 Apr 9;14(1):8321. doi: 10.1038/s41598-024-59093-5.
Endometrial fibrosis is the histologic appearance of intrauterine adhesion (IUA). Emerging evidences demonstrated umbilical cord mesenchymal stem cell-derived exosomes (UCMSC-exo) could alleviate endometrial fibrosis. But the specific mechanism is not clear. In this study, we explored the effect of UCMSC-exo on endometrial fibrosis, and investigated the possible role of miR-140-3p/FOXP1/Smad axis in anti-fibrotic properties of UCMSC-exo. UCMSC-exo were isolated and identified. Transforming growth factor-β (TGF-β) was used to induce human endometrial stromal cell (HESC) fibrosis. Dual luciferase assay was performed to verify the relationship between miR-140-3p and FOXP1. The expressions of fibrotic markers, SIP1, and p-Smad2/p-Smad3 in HESCs stimulated with UCMSC-exo were detected by western blot. In addition, the effects of miR-140-3p mimic, miR-140-3p inhibitor and FOXP1 over-expression on endometrial fibrosis were assessed. The isolated UCMSC-exo had a typical cup-shaped morphology and could be internalized into HESCs. The expressions of fibrotic markers were significantly increased by TGF-β, which was reversed by UCMSC-exo. MiR-140-3p in UCMSC-exo ameliorated TGf-β-induced HESCs fibrosis. FOXP1 was identified as the direct target of miR-140-3p, which could inversely regulate miR-140-3p's function on HESCs fibrosis. Furthermore, we demonstrated that miR-140-3p in UCMSC-exo regulated Smad signal pathway to exert the anti-fibrotic effect in HESCs. The anti-fibrotic effect of UCMSC-derived exosomes against HESC fibrosis was at least partially achieved by miR-140-3p/FOXP1/Smad axis.
子宫内膜纤维化是宫腔粘连（IUA）的组织学表现。新出现的证据表明，脐带间充质干细胞衍生的外泌体（UCMSC-exo）可以减轻子宫内膜纤维化。但具体机制尚不清楚。本研究探讨了 UCMSC-exo 对子宫内膜纤维化的影响，并研究了 miR-140-3p/FOXP1/Smad 轴在 UCMSC-exo 抗纤维化特性中的可能作用。分离并鉴定了 UCMSC-exo。用转化生长因子-β（TGF-β）诱导人子宫内膜基质细胞（HESC）纤维化。通过双荧光素酶报告基因实验验证 miR-140-3p 与 FOXP1 的关系。Western blot 检测 UCMSC-exo 刺激的 HESC 中纤维化标志物 SIP1 和 p-Smad2/p-Smad3 的表达。此外，还评估了 miR-140-3p 模拟物、miR-140-3p 抑制剂和 FOXP1 过表达对子宫内膜纤维化的影响。分离的 UCMSC-exo 呈典型的杯状形态，可被内化进入 HESC。TGF-β显著增加纤维化标志物的表达，而 UCMSC-exo 则逆转了这一作用。UCMSC-exo 中的 miR-140-3p 改善了 TGF-β诱导的 HESC 纤维化。FOXP1 被鉴定为 miR-140-3p 的直接靶标，可反向调节 miR-140-3p 对 HESC 纤维化的作用。此外，我们证明了 UCMSC-exo 中的 miR-140-3p 通过调节 Smad 信号通路在 HESC 中发挥抗纤维化作用。UCMSC 衍生的外泌体对 HESC 纤维化的抗纤维化作用至少部分是通过 miR-140-3p/FOXP1/Smad 轴实现的。
