Dataset Information

Umbilical cord mesenchymal stem cell-derived exosomes inhibits fibrosis in human endometrial stromal cells via miR-140-3p/FOXP1/Smad axis.

ABSTRACT: 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.

SUBMITTER: Song M

PROVIDER: S-EPMC11004014 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Umbilical cord mesenchymal stem cell-derived exosomes inhibits fibrosis in human endometrial stromal cells via miR-140-3p/FOXP1/Smad axis.

Song Mengling M Ma Lijun L Zhu Yongzhao Y Gao Huimin H Hu Rong R

Scientific reports 20240409 1

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 growt ...[more]

PMID: 38594471

Similar Datasets

Project description:BackgroundImpaired glucose metabolism and insulin sensitivity have been linked to the pathogenesis of gestational diabetes mellitus (GDM). Exosomes secreted by the umbilical cord mesenchymal stromal cells (UMSCs) and circular RNAs (circRNAs) derived from exosomes have been shown to be associated with the progression of GDM-related complications.MethodsUMSCs were isolated from umbilical cords and identified through flow cytometry. Exosomes were isolated from UMSCs and were then characterized. The expression levels of RNA of hsa_circ_0046060, mmu_circ_0002819, and miR-338-3p were determined by quantitative real-time polymerase chain reaction (RT-qPCR). The intracellular glucose intake and glycogen content were measured using a High Sensitivity Glucose Assay Kit and Glycogen Assay Kit, respectively. Bioinformatics analysis and luciferase reporter assay were used to validate interactions among hsa_circ_0046060, miR-338-3p, and G6PC2. The expression of insulin receptor substrate-1 (IRS-1) and its phosphorylated form, (p-IRS-1), as well as G6PC2, was determined through western blotting.ResultsUMSCs and exosomes were successfully isolated and identified. The upregulation of hsa_circ_0046060 decreased the intracellular glucose content in L-02 cells (43.45 vs. 16.87 pM/mg, P=0.0002), whereas shRNA-mediated downregulation reversed this effect (16.87 vs. 33.16 pM/mg, P=0.0011). Mmu_circ_0002819 in mice aggravated dysregulated glucose metabolism (49.88 vs. 21.69 pM/mg, P=0.0031) and insulin sensitivity (0.20 vs. 0.11 mg/mL, P=0.03) in GDM mice, which was abrogated by the knockdown of mmu_circ_0002819. The results of luciferase reporter assay revealed that miR-338-3p and G6PC2 were the potential targets of has_circ_0046060. Western blotting results showed that the reduced activation of IRS-1 induced by GDM (1.25 vs. 0.54, P=0.0001) could be rescued by the administration of si-circ-G-UMSC-EXOs (0.54 vs. 1.17, P=0.0001).ConclusionTaken together, the inhibition of hsa_circ_0046060 expression in exosomes from GDM-derived UMSCs can alleviate GDM by reversing abnormal glucose metabolism and insulin resistance in vivo and in vitro.

Dataset Information

Umbilical cord mesenchymal stem cell-derived exosomes inhibits fibrosis in human endometrial stromal cells via miR-140-3p/FOXP1/Smad axis.

Publications

Umbilical cord mesenchymal stem cell-derived exosomes inhibits fibrosis in human endometrial stromal cells via miR-140-3p/FOXP1/Smad axis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets